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\n  \n 2024\n \n \n (1)\n \n \n
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\n \n\n \n \n \n \n \n The mechanisms of nanoparticle delivery to solid tumours.\n \n \n \n\n\n \n Nguyen, L. N., Ngo, W., Lin, Z. P, Sindhwani, S., MacMillan, P., Mladjenovic, S. M, & Chan, W. C.\n\n\n \n\n\n\n Nature Reviews Bioengineering,1–13. 2024.\n \n\n\n\n
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@article{nguyen2024mechanisms,\n  title={The mechanisms of nanoparticle delivery to solid tumours},\n  author={Nguyen, Luan NM and Ngo, Wayne and Lin, Zachary P and Sindhwani, Shrey and MacMillan, Presley and Mladjenovic, Stefan M and Chan, Warren CW},\n  journal={Nature Reviews Bioengineering},\n  pages={1--13},\n  year={2024},\n  publisher={Nature Publishing Group UK London}\n}\n\n\n
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\n  \n 2023\n \n \n (7)\n \n \n
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\n \n\n \n \n \n \n \n \n The exit of nanoparticles from solid tumours.\n \n \n \n \n\n\n \n Nguyen, L. N., Lin, Z. P, Sindhwani, S., MacMillan, P., Mladjenovic, S. M, Stordy, B., Ngo, W., & Chan, W. C.\n\n\n \n\n\n\n Nature Materials,1–12. 2023.\n PMID: 37592029\n\n\n\n
\n\n\n\n \n \n \"ThePaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 17 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{nguyen2023exit,\n  title={The exit of nanoparticles from solid tumours},\n  author={Nguyen, Luan NM and Lin, Zachary P and Sindhwani, Shrey and MacMillan, Presley and Mladjenovic, Stefan M and Stordy, Benjamin and Ngo, Wayne and Chan, Warren CW},\n  journal={Nature Materials},\n  pages={1--12},\n  abstract = { Nanoparticles enter tumours through endothelial cells, gaps or other mechanisms, but how they exit is unclear. The current paradigm states that collapsed tumour lymphatic vessels impair the exit of nanoparticles and lead to enhanced retention. Here we show that nanoparticles exit the tumour through the lymphatic vessels within or surrounding the tumour. The dominant lymphatic exit mechanism depends on the nanoparticle size. Nanoparticles that exit the tumour through the lymphatics are returned to the blood system, allowing them to recirculate and interact with the tumour in another pass. Our results enable us to define a mechanism of nanoparticle delivery to solid tumours alternative to the enhanced permeability and retention effect. We call this mechanism the active transport and retention principle. This delivery principle provides a new framework to engineer nanomedicines for cancer treatment and detection.},\n  year={2023},\n  publisher={Nature Publishing Group UK London},\n  doi = {https://doi.org/10.1038/s41563-023-01630-0},\n    note ={PMID: 37592029},\n  URL = {https://www.nature.com/articles/s41563-023-01630-0},\n}\n\n\n
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\n Nanoparticles enter tumours through endothelial cells, gaps or other mechanisms, but how they exit is unclear. The current paradigm states that collapsed tumour lymphatic vessels impair the exit of nanoparticles and lead to enhanced retention. Here we show that nanoparticles exit the tumour through the lymphatic vessels within or surrounding the tumour. The dominant lymphatic exit mechanism depends on the nanoparticle size. Nanoparticles that exit the tumour through the lymphatics are returned to the blood system, allowing them to recirculate and interact with the tumour in another pass. Our results enable us to define a mechanism of nanoparticle delivery to solid tumours alternative to the enhanced permeability and retention effect. We call this mechanism the active transport and retention principle. This delivery principle provides a new framework to engineer nanomedicines for cancer treatment and detection.\n
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\n \n\n \n \n \n \n \n \n Toward Predicting Nanoparticle Distribution in Heterogeneous Tumor Tissues.\n \n \n \n \n\n\n \n MacMillan, P., Syed, A. M., Kingston, B. R., Ngai, J., Sindhwani, S., Lin, Z. P., Nguyen, L. N. M., Ngo, W., Mladjenovic, S. M., Ji, Q., Blackadar, C., & Chan, W. C. W.\n\n\n \n\n\n\n Nano Letters, 23(15): 7197-7205. 2023.\n PMID: 37506224\n\n\n\n
\n\n\n\n \n \n \"TowardPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{doi:10.1021/acs.nanolett.3c02186,\nauthor = {MacMillan, Presley and Syed, Abdullah M. and Kingston, Benjamin R. and Ngai, Jessica and Sindhwani, Shrey and Lin, Zachary P. and Nguyen, Luan N. M. and Ngo, Wayne and Mladjenovic, Stefan M. and Ji, Qin and Blackadar, Colin and Chan, Warren C. W.},\ntitle = {Toward Predicting Nanoparticle Distribution in Heterogeneous Tumor Tissues},\njournal = {Nano Letters},\nvolume = {23},\nnumber = {15},\npages = {7197-7205},\nyear = {2023},\ndoi = {10.1021/acs.nanolett.3c02186},\n    note ={PMID: 37506224},\n\nURL = { \n        https://doi.org/10.1021/acs.nanolett.3c02186\n    \n},\neprint = { \n        https://doi.org/10.1021/acs.nanolett.3c02186\n    \n}\n,\n    abstract = { Nanobio interaction studies have generated a significant amount of data. An important next step is to organize the data and design computational techniques to analyze the nanobio interactions. Here we developed a computational technique to correlate the nanoparticle spatial distribution within heterogeneous solid tumors. This approach led to greater than 88\\% predictive accuracy of nanoparticle location within a tumor tissue. This proof-of-concept study shows that tumor heterogeneity might be defined computationally by the patterns of biological structures within the tissue, enabling the identification of tumor patterns for nanoparticle accumulation. }\n}\n\n\n\n\n
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\n Nanobio interaction studies have generated a significant amount of data. An important next step is to organize the data and design computational techniques to analyze the nanobio interactions. Here we developed a computational technique to correlate the nanoparticle spatial distribution within heterogeneous solid tumors. This approach led to greater than 88% predictive accuracy of nanoparticle location within a tumor tissue. This proof-of-concept study shows that tumor heterogeneity might be defined computationally by the patterns of biological structures within the tissue, enabling the identification of tumor patterns for nanoparticle accumulation. \n
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\n \n\n \n \n \n \n \n \n Genotyping SARS-CoV-2 Variants Using Ratiometric Nucleic Acid Barcode Panels.\n \n \n \n \n\n\n \n Kozlowski, H. N., Malekjahani, A., Li, V. Y. C., Lekuti, A. A., Perusini, S., Bell, N. G., Voisin, V., Pouyabahar, D., Pai, S., Bader, G. D., Mubareka, S., Gubbay, J. B., & Chan, W. C. W.\n\n\n \n\n\n\n Analytical Chemistry, 95(14): 5877-5885. 2023.\n PMID: 37000033\n\n\n\n
\n\n\n\n \n \n \"GenotypingPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{doi:10.1021/acs.analchem.2c04630,\nauthor = {Kozlowski, Hannah N. and Malekjahani, Ayden and Li, Vanessa Y. C. and Lekuti, Ayokunle A. and Perusini, Stephen and Bell, Natalie G. and Voisin, Veronique and Pouyabahar, Delaram and Pai, Shraddha and Bader, Gary D. and Mubareka, Samira and Gubbay, Jonathan B. and Chan, Warren C. W.},\ntitle = {Genotyping SARS-CoV-2 Variants Using Ratiometric Nucleic Acid Barcode Panels},\njournal = {Analytical Chemistry},\nvolume = {95},\nnumber = {14},\npages = {5877-5885},\nyear = {2023},\ndoi = {10.1021/acs.analchem.2c04630},\n    note ={PMID: 37000033},\n\nURL = { \n        https://doi.org/10.1021/acs.analchem.2c04630\n    \n},\neprint = { \n        https://doi.org/10.1021/acs.analchem.2c04630\n    \n}\n,\n    abstract = { Designing diagnostic assays to genotype rapidly mutating viruses remains a challenge despite the overall improvements in nucleic acid detection technologies. RT-PCR and next-generation sequencing are unsuitable for genotyping during outbreaks or in point-of-care detection due to their infrastructure requirements and longer turnaround times. We developed a quantum dot barcode multiplexing system to genotype mutated viruses. We designed multiple quantum dot barcodes to target conserved, wildtype, and mutated regions of SARS-CoV-2. We calculated ratios of the signal output from different barcodes that enabled SARS-CoV-2 detection and identified SARS-CoV-2 variant strains from a sample. We detected different sequence types, including conserved genes, nucleotide deletions, and single nucleotide substitutions. Our system detected SARS-CoV-2 patient specimens with 98\\% sensitivity and 94\\% specificity across 91 patient samples. Further, we leveraged our barcoding and ratio system to track the emergence of the N501Y SARS-CoV-2 mutation from December 2020 to May 2021 and demonstrated that the more transmissible N501Y mutation started to dominate infections by April 2021. Our barcoding and signal ratio approach can genotype viruses and track the emergence of viral mutations in a single diagnostic test. This technology can be extended to tracking other viruses. Combined with smartphone detection technologies, this assay can be adapted for point-of-care tracking of viral mutations in real time. }\n}\n\n\n\n\n
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\n Designing diagnostic assays to genotype rapidly mutating viruses remains a challenge despite the overall improvements in nucleic acid detection technologies. RT-PCR and next-generation sequencing are unsuitable for genotyping during outbreaks or in point-of-care detection due to their infrastructure requirements and longer turnaround times. We developed a quantum dot barcode multiplexing system to genotype mutated viruses. We designed multiple quantum dot barcodes to target conserved, wildtype, and mutated regions of SARS-CoV-2. We calculated ratios of the signal output from different barcodes that enabled SARS-CoV-2 detection and identified SARS-CoV-2 variant strains from a sample. We detected different sequence types, including conserved genes, nucleotide deletions, and single nucleotide substitutions. Our system detected SARS-CoV-2 patient specimens with 98% sensitivity and 94% specificity across 91 patient samples. Further, we leveraged our barcoding and ratio system to track the emergence of the N501Y SARS-CoV-2 mutation from December 2020 to May 2021 and demonstrated that the more transmissible N501Y mutation started to dominate infections by April 2021. Our barcoding and signal ratio approach can genotype viruses and track the emergence of viral mutations in a single diagnostic test. This technology can be extended to tracking other viruses. Combined with smartphone detection technologies, this assay can be adapted for point-of-care tracking of viral mutations in real time. \n
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\n \n\n \n \n \n \n \n \n Principles of Nanoparticle Delivery to Solid Tumors.\n \n \n \n \n\n\n \n Chan, W. C. W.\n\n\n \n\n\n\n BME Frontiers, 4: 0016. 2023.\n \n\n\n\n
\n\n\n\n \n \n \"PrinciplesPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 13 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{\ndoi:10.34133/bmef.0016,\nauthor = {Warren C. W. Chan },\ntitle = {Principles of Nanoparticle Delivery to Solid Tumors},\njournal = {BME Frontiers},\nvolume = {4},\nnumber = {},\npages = {0016},\nyear = {2023},\ndoi = {10.34133/bmef.0016},\nURL = {https://spj.science.org/doi/abs/10.34133/bmef.0016},\neprint = {https://spj.science.org/doi/pdf/10.34133/bmef.0016},\nabstract = {The effective treatment of patients with cancer hinges on the delivery of therapeutics to a tumor site. Nanoparticles provide an essential transport system. We present 5 principles to consider when designing nanoparticles for cancer targeting: (a) Nanoparticles acquire biological identity in vivo, (b) organs compete for nanoparticles in circulation, (c) nanoparticles must enter solid tumors to target tumor components, (d) nanoparticles must navigate the tumor microenvironment for cellular or organelle targeting, and (e) size, shape, surface chemistry, and other physicochemical properties of nanoparticles influence their transport process to the target. This review article describes these principles and their application for engineering nanoparticle delivery systems to carry therapeutics to tumors or other disease targets.}}\n\n\n\n
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\n The effective treatment of patients with cancer hinges on the delivery of therapeutics to a tumor site. Nanoparticles provide an essential transport system. We present 5 principles to consider when designing nanoparticles for cancer targeting: (a) Nanoparticles acquire biological identity in vivo, (b) organs compete for nanoparticles in circulation, (c) nanoparticles must enter solid tumors to target tumor components, (d) nanoparticles must navigate the tumor microenvironment for cellular or organelle targeting, and (e) size, shape, surface chemistry, and other physicochemical properties of nanoparticles influence their transport process to the target. This review article describes these principles and their application for engineering nanoparticle delivery systems to carry therapeutics to tumors or other disease targets.\n
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\n \n\n \n \n \n \n \n \n Writing Excellent Review Articles.\n \n \n \n \n\n\n \n Chan, W. C. W.\n\n\n \n\n\n\n ACS Nano, 17(3): 1723-1724. 2023.\n PMID: 36788673\n\n\n\n
\n\n\n\n \n \n \"WritingPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n  \n \n 10 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{doi:10.1021/acsnano.3c00497,\nauthor = {Chan, Warren C. W.},\ntitle = {Writing Excellent Review Articles},\njournal = {ACS Nano},\nvolume = {17},\nnumber = {3},\npages = {1723-1724},\nyear = {2023},\ndoi = {10.1021/acsnano.3c00497},\n    note ={PMID: 36788673},\n\nURL = { \n        https://doi.org/10.1021/acsnano.3c00497\n    \n},\neprint = { \n        https://doi.org/10.1021/acsnano.3c00497\n    \n}\n\n}\n\n\n\n\n
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\n \n\n \n \n \n \n \n \n Nanoparticles Bind to Endothelial Cells in Injured Blood Vessels via a Transient Protein Corona.\n \n \n \n \n\n\n \n Lin, Z. P., Ngo, W., Mladjenovic, S. M., Wu, J. L. Y., & Chan, W. C. W.\n\n\n \n\n\n\n Nano Letters, 23(3): 1003-1009. 2023.\n PMID: 36692977\n\n\n\n
\n\n\n\n \n \n \"NanoparticlesPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{doi:10.1021/acs.nanolett.2c04501,\nauthor = {Lin, Zachary P. and Ngo, Wayne and Mladjenovic, Stefan M. and Wu, Jamie L. Y. and Chan, Warren C. W.},\ntitle = {Nanoparticles Bind to Endothelial Cells in Injured Blood Vessels via a Transient Protein Corona},\njournal = {Nano Letters},\nvolume = {23},\nnumber = {3},\npages = {1003-1009},\nyear = {2023},\ndoi = {10.1021/acs.nanolett.2c04501},\n    note ={PMID: 36692977},\n\nURL = { \n        https://doi.org/10.1021/acs.nanolett.2c04501\n    \n},\neprint = { \n        https://doi.org/10.1021/acs.nanolett.2c04501\n    \n}\n,\n    abstract = { Nanoparticles travel through blood vessels to reach disease sites, but the local environment they encounter may affect their surface chemistry and cellular interactions. Here, we found that as nanoparticles transit through injured blood vessels they may interact with a highly localized concentration of platelet factor 4 proteins released from activated platelets. The platelet factor 4 binds to the nanoparticle surface and interacts with heparan sulfate proteoglycans on endothelial cells, and induces uptake. Understanding nanoparticle interactions with blood proteins and endothelial cells during circulation is critical to optimizing their design for diseased tissue targeting and delivery. }\n}\n\n\n\n\n\n
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\n Nanoparticles travel through blood vessels to reach disease sites, but the local environment they encounter may affect their surface chemistry and cellular interactions. Here, we found that as nanoparticles transit through injured blood vessels they may interact with a highly localized concentration of platelet factor 4 proteins released from activated platelets. The platelet factor 4 binds to the nanoparticle surface and interacts with heparan sulfate proteoglycans on endothelial cells, and induces uptake. Understanding nanoparticle interactions with blood proteins and endothelial cells during circulation is critical to optimizing their design for diseased tissue targeting and delivery. \n
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\n \n\n \n \n \n \n \n \n Delineating the tumour microenvironment response to a lipid nanoparticle formulation.\n \n \n \n \n\n\n \n Ngai, J., MacMillan, P., Kingston, B. R., Lin, Z. P., Ouyang, B., & Chan, W. C.\n\n\n \n\n\n\n Journal of Controlled Release, 353: 988-1001. 2023.\n \n\n\n\n
\n\n\n\n \n \n \"DelineatingPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{NGAI2023988,\ntitle = {Delineating the tumour microenvironment response to a lipid nanoparticle formulation},\njournal = {Journal of Controlled Release},\nvolume = {353},\npages = {988-1001},\nyear = {2023},\nissn = {0168-3659},\ndoi = {https://doi.org/10.1016/j.jconrel.2022.12.021},\nurl = {https://www.sciencedirect.com/science/article/pii/S0168365922008355},\nauthor = {Jessica Ngai and Presley MacMillan and Benjamin R. Kingston and Zachary P. Lin and Ben Ouyang and Warren C.W. Chan},\nkeywords = {Cancer, Doxil, Doxorubicin, Liposomes, Cytodistribution, Flow cytometry},\nabstract = {Nanoparticles can reduce cytotoxicity, increase circulation time and increase accumulation in tumours compared to free drug. However, the value of using nanoparticles for carrying small molecules to treat tumours at the cellular level has been poorly established. Here we conducted a cytodistribution analysis on Doxorubicin-treated and Doxil-treated tumours to delineate the differences between the small molecule therapeutic Doxorubicin and its packaged liposomal formulation Doxil. We found that Doxil kills more cancer cells, macrophages and neutrophils in the 4T1 breast cancer tumour model, but there is delayed killing compared to its small molecule counterpart Doxorubicin. The cellular interaction with Doxil has slower uptake kinetics and the particles must be degraded to release the drug and kill the cells. We also found that macrophages and neutrophils in Doxil-treated tumours repopulated faster than cancer cells during the relapse phase. While researchers conventionally use tumour volume and animal survival to determine a therapeutic effect, our results show diverse cell killing and a greater amount of cell death in vivo after Doxil liposomes are administered. We conclude that the fate and behaviour of the nanocarrier influences its effectiveness as a cancer therapy. Further investigations on the interactions between different nanoparticle designs and the tumour microenvironment components will lead to more precise engineering of nanocarriers to selectively kill tumour cells and prolong the therapeutic effect.}\n}\n\n\n
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\n Nanoparticles can reduce cytotoxicity, increase circulation time and increase accumulation in tumours compared to free drug. However, the value of using nanoparticles for carrying small molecules to treat tumours at the cellular level has been poorly established. Here we conducted a cytodistribution analysis on Doxorubicin-treated and Doxil-treated tumours to delineate the differences between the small molecule therapeutic Doxorubicin and its packaged liposomal formulation Doxil. We found that Doxil kills more cancer cells, macrophages and neutrophils in the 4T1 breast cancer tumour model, but there is delayed killing compared to its small molecule counterpart Doxorubicin. The cellular interaction with Doxil has slower uptake kinetics and the particles must be degraded to release the drug and kill the cells. We also found that macrophages and neutrophils in Doxil-treated tumours repopulated faster than cancer cells during the relapse phase. While researchers conventionally use tumour volume and animal survival to determine a therapeutic effect, our results show diverse cell killing and a greater amount of cell death in vivo after Doxil liposomes are administered. We conclude that the fate and behaviour of the nanocarrier influences its effectiveness as a cancer therapy. Further investigations on the interactions between different nanoparticle designs and the tumour microenvironment components will lead to more precise engineering of nanocarriers to selectively kill tumour cells and prolong the therapeutic effect.\n
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\n \n\n \n \n \n \n \n \n Sequential Reagent Release from a Layered Tablet for Multistep Diagnostic Assays.\n \n \n \n \n\n\n \n Li, V. Y. C., Udugama, B., Kadhiresan, P., & Chan, W. C. W.\n\n\n \n\n\n\n Analytical Chemistry, 94(49): 17102-17111. 2022.\n PMID: 36454606\n\n\n\n
\n\n\n\n \n \n \"SequentialPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{doi:10.1021/acs.analchem.2c03315,\nauthor = {Li, Vanessa Y. C. and Udugama, Buddhisha and Kadhiresan, Pranav and Chan, Warren C. W.},\ntitle = {Sequential Reagent Release from a Layered Tablet for Multistep Diagnostic Assays},\njournal = {Analytical Chemistry},\nvolume = {94},\nnumber = {49},\npages = {17102-17111},\nyear = {2022},\ndoi = {10.1021/acs.analchem.2c03315},\n    note ={PMID: 36454606},\n\nURL = { \n        https://doi.org/10.1021/acs.analchem.2c03315\n    \n},\neprint = { \n        https://doi.org/10.1021/acs.analchem.2c03315\n    \n}\n,\n    abstract = { Diagnostic assays are commonly performed in multiple steps, where reagents are added at specific times and concentrations into a reaction chamber. The reagents require storage, preparation, and addition in the correct sequence and amount. These steps rely on trained technicians and instrumentation to perform each task. The reliance on such resources hinders the use of these diagnostic assays by lay users. We developed a tablet that can sequentially introduce prequantified lyophilized diagnostic reagents at specific time points for a multistep assay. We designed the tablet to have multiple layers using cellulose-grade polymers, such as microcrystalline cellulose and hydroxypropyl cellulose. Our formulation allows each layer to dissolve at a controlled rate to introduce reagents into the solution sequentially. The release rate is controlled by modulating the compression force or chemical formulation of the layer. Controlling the reagent release time is important because different assays have specific times when reagents need to be added. As proof of concept, we demonstrated two different assays with our tablet system. Our tablet detected nucleic acid target (tpp47 gene from Treponema pallidum) and nitrite ions in an aqueous sample without user intervention. Our multilayer tablets can simplify multistep assay processes. }\n}\n\n\n
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\n Diagnostic assays are commonly performed in multiple steps, where reagents are added at specific times and concentrations into a reaction chamber. The reagents require storage, preparation, and addition in the correct sequence and amount. These steps rely on trained technicians and instrumentation to perform each task. The reliance on such resources hinders the use of these diagnostic assays by lay users. We developed a tablet that can sequentially introduce prequantified lyophilized diagnostic reagents at specific time points for a multistep assay. We designed the tablet to have multiple layers using cellulose-grade polymers, such as microcrystalline cellulose and hydroxypropyl cellulose. Our formulation allows each layer to dissolve at a controlled rate to introduce reagents into the solution sequentially. The release rate is controlled by modulating the compression force or chemical formulation of the layer. Controlling the reagent release time is important because different assays have specific times when reagents need to be added. As proof of concept, we demonstrated two different assays with our tablet system. Our tablet detected nucleic acid target (tpp47 gene from Treponema pallidum) and nitrite ions in an aqueous sample without user intervention. Our multilayer tablets can simplify multistep assay processes. \n
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\n \n\n \n \n \n \n \n \n Identifying cell receptors for the nanoparticle protein corona using genome screens.\n \n \n \n \n\n\n \n Ngo, W., Wu, J. L. Y., Lin, Z. P., Zhang, Y., Bussin, B., Granda Farias, A., Syed, A. M., Chan, K., Habsid, A., Moffat, J., & Chan, W. C. W.\n\n\n \n\n\n\n Nature Chemical Biology. Aug 2022.\n \n\n\n\n
\n\n\n\n \n \n \"IdentifyingPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 30 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@Article{Ngo2022,\nauthor={Ngo, Wayne\nand Wu, Jamie L. Y.\nand Lin, Zachary P.\nand Zhang, Yuwei\nand Bussin, Bram\nand Granda Farias, Adrian\nand Syed, Abdullah M.\nand Chan, Katherine\nand Habsid, Andrea\nand Moffat, Jason\nand Chan, Warren C. W.},\ntitle={Identifying cell receptors for the nanoparticle protein corona using genome screens},\njournal={Nature Chemical Biology},\nyear={2022},\nmonth={Aug},\nday={11},\nabstract={Nanotechnology provides platforms to deliver medical agents to specific cells. However, the nanoparticle's surface becomes covered with serum proteins in the blood after administration despite engineering efforts to protect it with targeting or blocking molecules. Here, we developed a strategy to identify the main interactions between nanoparticle-adsorbed proteins and a cell by integrating mass spectrometry with pooled genome screens and Search Tool for the Retrieval of Interacting Genes analysis. We found that the low-density lipoprotein (LDL) receptor was responsible for approximately 75{\\%} of serum-coated gold nanoparticle uptake in U-87 MG cells. Apolipoprotein B and complement C8 proteins on the nanoparticle mediated uptake through the LDL receptor. In vivo, nanoparticle accumulation correlated with LDL receptor expression in the organs of mice. A detailed understanding of how adsorbed serum proteins bind to cell receptors will lay the groundwork for controlling the delivery of nanoparticles at the molecular level to diseased tissues for therapeutic and diagnostic applications.},\nissn={1552-4469},\ndoi={10.1038/s41589-022-01093-5},\nurl={https://doi.org/10.1038/s41589-022-01093-5}\n}\n\n\n\n
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\n Nanotechnology provides platforms to deliver medical agents to specific cells. However, the nanoparticle's surface becomes covered with serum proteins in the blood after administration despite engineering efforts to protect it with targeting or blocking molecules. Here, we developed a strategy to identify the main interactions between nanoparticle-adsorbed proteins and a cell by integrating mass spectrometry with pooled genome screens and Search Tool for the Retrieval of Interacting Genes analysis. We found that the low-density lipoprotein (LDL) receptor was responsible for approximately 75% of serum-coated gold nanoparticle uptake in U-87 MG cells. Apolipoprotein B and complement C8 proteins on the nanoparticle mediated uptake through the LDL receptor. In vivo, nanoparticle accumulation correlated with LDL receptor expression in the organs of mice. A detailed understanding of how adsorbed serum proteins bind to cell receptors will lay the groundwork for controlling the delivery of nanoparticles at the molecular level to diseased tissues for therapeutic and diagnostic applications.\n
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\n \n\n \n \n \n \n \n \n A proposed mathematical description of in vivo nanoparticle delivery.\n \n \n \n \n\n\n \n Wu, J. L., Stordy, B. P., Nguyen, L. N., Deutschman, C. P., & Chan, W. C.\n\n\n \n\n\n\n Advanced Drug Delivery Reviews, 189: 114520. 2022.\n \n\n\n\n
\n\n\n\n \n \n \"APaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{WU2022114520,\ntitle = {A proposed mathematical description of in vivo nanoparticle delivery},\njournal = {Advanced Drug Delivery Reviews},\nvolume = {189},\npages = {114520},\nyear = {2022},\nissn = {0169-409X},\ndoi = {https://doi.org/10.1016/j.addr.2022.114520},\nurl = {https://www.sciencedirect.com/science/article/pii/S0169409X22004100},\nauthor = {Jamie L.Y. Wu and Benjamin P. Stordy and Luan N.M. Nguyen and Christopher P. Deutschman and Warren C.W. Chan},\nkeywords = {Nanoparticles, Targeting, Drug delivery, Nano-bio interactions},\nabstract = {Nanoparticles are promising vehicles for the precise delivery of molecular therapies to diseased sites. Nanoparticles interact with a series of tissues and cells before they reach their target, which causes less than 1% of administered nanoparticles to be delivered to these target sites. Researchers have been studying the nano-bio interactions that mediate nanoparticle delivery to develop guidelines for designing nanoparticles with enhanced delivery properties. In this review article, we describe these nano-bio interactions with a series of mathematical equations that quantitatively define the nanoparticle delivery process. We employ a compartment model framework to describe delivery where nanoparticles are either (1) at the site of administration, (2) in the vicinity of target cells, (3) internalized by the target cells, or (4) sequestered away in off-target sites or eliminated from the body. This framework explains how different biological processes govern nanoparticle transport between these compartments, and the role of intercompartmental transport rates in determining the final nanoparticle delivery efficiency. Our framework provides guiding principles to engineer nanoparticles for improved targeted delivery.}\n}\n\n\n\n\n\n\n
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\n Nanoparticles are promising vehicles for the precise delivery of molecular therapies to diseased sites. Nanoparticles interact with a series of tissues and cells before they reach their target, which causes less than 1% of administered nanoparticles to be delivered to these target sites. Researchers have been studying the nano-bio interactions that mediate nanoparticle delivery to develop guidelines for designing nanoparticles with enhanced delivery properties. In this review article, we describe these nano-bio interactions with a series of mathematical equations that quantitatively define the nanoparticle delivery process. We employ a compartment model framework to describe delivery where nanoparticles are either (1) at the site of administration, (2) in the vicinity of target cells, (3) internalized by the target cells, or (4) sequestered away in off-target sites or eliminated from the body. This framework explains how different biological processes govern nanoparticle transport between these compartments, and the role of intercompartmental transport rates in determining the final nanoparticle delivery efficiency. Our framework provides guiding principles to engineer nanoparticles for improved targeted delivery.\n
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\n \n\n \n \n \n \n \n \n Conjugating Ligands to an Equilibrated Nanoparticle Protein Corona Enables Cell Targeting in Serum.\n \n \n \n \n\n\n \n Stordy, B., Zhang, Y., Sepahi, Z., Khatami, M. H., Kim, P. M., & Chan, W. C. W.\n\n\n \n\n\n\n Chemistry of Materials, 34(15): 6868-6882. 2022.\n \n\n\n\n
\n\n\n\n \n \n \"ConjugatingPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 10 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{doi:10.1021/acs.chemmater.2c01168,\nauthor = {Stordy, Benjamin and Zhang, Yuwei and Sepahi, Zahra and Khatami, Mohammad Hassan and Kim, Philip M. and Chan, Warren C. W.},\ntitle = {Conjugating Ligands to an Equilibrated Nanoparticle Protein Corona Enables Cell Targeting in Serum},\njournal = {Chemistry of Materials},\nvolume = {34},\nnumber = {15},\npages = {6868-6882},\nyear = {2022},\nabstract={Targeting ligands are conjugated onto nanoparticles to increase their selectivity for diseased cells. However, they become covered by serum proteins which prevent them from binding to target receptors. Here, we show that the nanoparticle protein corona achieved a maximum thickness in serum because the protein adsorption and desorption rates reached an equilibrium. Simulation experiments suggest that the number of molecular interactions between proteins decrease with distance from the nanoparticle surface until the forces are too weak to hold the proteins together. This results in an equilibration state between the proteins on the nanoparticle surface and in biological fluids. Conjugating targeting ligands to this equilibrated protein corona allowed the nanoparticles to bind to target cells in the presence of serum proteins. In contrast, conjugating targeting ligands directly to the nanoparticle surface resulted in a 55% reduction in binding to target cells in serum. We demonstrated this concept using two nanoparticle material types with different surface chemistries. We present a ligand-on-corona conjugation strategy that overcomes the negative impact of serum protein adsorption on nanoparticle cellular targeting.},\ndoi = {10.1021/acs.chemmater.2c01168},\n\nURL = { \n        https://doi.org/10.1021/acs.chemmater.2c01168\n    \n},\neprint = { \n        https://doi.org/10.1021/acs.chemmater.2c01168\n    \n}\n\n}\n\n\n\n\n\n
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\n Targeting ligands are conjugated onto nanoparticles to increase their selectivity for diseased cells. However, they become covered by serum proteins which prevent them from binding to target receptors. Here, we show that the nanoparticle protein corona achieved a maximum thickness in serum because the protein adsorption and desorption rates reached an equilibrium. Simulation experiments suggest that the number of molecular interactions between proteins decrease with distance from the nanoparticle surface until the forces are too weak to hold the proteins together. This results in an equilibration state between the proteins on the nanoparticle surface and in biological fluids. Conjugating targeting ligands to this equilibrated protein corona allowed the nanoparticles to bind to target cells in the presence of serum proteins. In contrast, conjugating targeting ligands directly to the nanoparticle surface resulted in a 55% reduction in binding to target cells in serum. We demonstrated this concept using two nanoparticle material types with different surface chemistries. We present a ligand-on-corona conjugation strategy that overcomes the negative impact of serum protein adsorption on nanoparticle cellular targeting.\n
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\n \n\n \n \n \n \n \n \n Macrophages Actively Transport Nanoparticles in Tumors After Extravasation.\n \n \n \n \n\n\n \n Lin, Z. P., Nguyen, L. N. M., Ouyang, B., MacMillan, P., Ngai, J., Kingston, B. R., Mladjenovic, S. M., & Chan, W. C. W.\n\n\n \n\n\n\n ACS Nano. April 2022.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"MacrophagesPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 11 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{lin_macrophages_2022,\n\ttitle = {Macrophages {Actively} {Transport} {Nanoparticles} in {Tumors} {After} {Extravasation}},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.1c11578},\n\tdoi = {10.1021/acsnano.1c11578},\n\tabstract = {Nanoparticles need to navigate a complex microenvironment to target cells in solid tumors after extravasation. Diffusion is currently the accepted primary mechanism for nanoparticle distribution in tumors. However, the extracellular matrix can limit nanoparticle diffusion. Here, we identified tumor-associated macrophages as another key player in transporting and redistributing nanoparticles in the tumor microenvironment. We found tumor-associated macrophages actively migrate toward nanoparticles extravasated from the vessels, engulfing and redistributing them in the tumor stroma. The macrophages can carry the nanoparticles 2–5 times deeper in the tumor than passive diffusion. The amount of nanoparticles transported by the tumor-associated macrophages is size-dependent. Understanding the nanoparticle behavior after extravasation will provide strategies to engineer them to navigate the microenvironment for improved intratumoral targeting and therapeutic effectiveness.},\n\turldate = {2022-04-25},\n\tjournal = {ACS Nano},\n\tauthor = {Lin, Zachary Pengju and Nguyen, Luan N. M. and Ouyang, Ben and MacMillan, Presley and Ngai, Jessica and Kingston, Benjamin R. and Mladjenovic, Stefan M. and Chan, Warren C. W.},\n\tmonth = apr,\n\tyear = {2022},\n\tnote = {Publisher: American Chemical Society},\n}\n\n
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\n Nanoparticles need to navigate a complex microenvironment to target cells in solid tumors after extravasation. Diffusion is currently the accepted primary mechanism for nanoparticle distribution in tumors. However, the extracellular matrix can limit nanoparticle diffusion. Here, we identified tumor-associated macrophages as another key player in transporting and redistributing nanoparticles in the tumor microenvironment. We found tumor-associated macrophages actively migrate toward nanoparticles extravasated from the vessels, engulfing and redistributing them in the tumor stroma. The macrophages can carry the nanoparticles 2–5 times deeper in the tumor than passive diffusion. The amount of nanoparticles transported by the tumor-associated macrophages is size-dependent. Understanding the nanoparticle behavior after extravasation will provide strategies to engineer them to navigate the microenvironment for improved intratumoral targeting and therapeutic effectiveness.\n
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\n \n\n \n \n \n \n \n \n Gold Nanoparticle Smartphone Platform for Diagnosing Urinary Tract Infections.\n \n \n \n \n\n\n \n Zagorovsky, K., Fernández-Argüelles, M. T., Bona, D., Elshawadfy, A. M., Syed, A. M., Kadhiresan, P., Mazzulli, T., Maxwell, K. L., & Chan, W. C.\n\n\n \n\n\n\n ACS Nanoscience Au. April 2022.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"GoldPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{zagorovsky_gold_2022,\n\ttitle = {Gold {Nanoparticle} {Smartphone} {Platform} for {Diagnosing} {Urinary} {Tract} {Infections}},\n\turl = {https://doi.org/10.1021/acsnanoscienceau.2c00001},\n\tdoi = {10.1021/acsnanoscienceau.2c00001},\n\tabstract = {Current urinary tract infection (UTI) diagnostic methods are slow or provide limited information, resulting in prescribing antibiotic therapy before bacterial pathogen identification. Here, we adapted a gold nanoparticle colorimetric approach and developed a smartphone platform for UTI detection. We show the parallel identification of five major UTI pathogens at clinically relevant concentrations of 105 bacteria/mL using bacteria-specific and universal probes. We validated the diagnostic technology using 115 positive and 19 negative samples from patients with Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae infections. The assay successfully identified the infecting pathogen (specificity: {\\textgreater}98\\% and sensitivity: 51–73\\%) in 3 h. Our platform is faster than culturing and can wirelessly store and transmit results at the cost of \\$0.38 per assay.},\n\turldate = {2022-04-25},\n\tjournal = {ACS Nanoscience Au},\n\tauthor = {Zagorovsky, Kyryl and Fernández-Argüelles, Maria Teresa and Bona, Diane and Elshawadfy, Ashraf Mohamed and Syed, Abdullah Muhammad and Kadhiresan, Pranav and Mazzulli, Tony and Maxwell, Karen L. and Chan, Warren C.W.},\n\tmonth = apr,\n\tyear = {2022},\n\tnote = {Publisher: American Chemical Society},\n}\n\n
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\n Current urinary tract infection (UTI) diagnostic methods are slow or provide limited information, resulting in prescribing antibiotic therapy before bacterial pathogen identification. Here, we adapted a gold nanoparticle colorimetric approach and developed a smartphone platform for UTI detection. We show the parallel identification of five major UTI pathogens at clinically relevant concentrations of 105 bacteria/mL using bacteria-specific and universal probes. We validated the diagnostic technology using 115 positive and 19 negative samples from patients with Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae infections. The assay successfully identified the infecting pathogen (specificity: \\textgreater98% and sensitivity: 51–73%) in 3 h. Our platform is faster than culturing and can wirelessly store and transmit results at the cost of $0.38 per assay.\n
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\n \n\n \n \n \n \n \n \n Why nanoparticles prefer liver macrophage cell uptake in vivo.\n \n \n \n \n\n\n \n Ngo, W., Ahmed, S., Blackadar, C., Bussin, B., Ji, Q., Mladjenovic, S. M., Sepahi, Z., & Chan, W. C. W.\n\n\n \n\n\n\n Advanced Drug Delivery Reviews, 185: 114238. June 2022.\n \n\n\n\n
\n\n\n\n \n \n \"WhyPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{ngo_why_2022,\n\ttitle = {Why nanoparticles prefer liver macrophage cell uptake in vivo},\n\tvolume = {185},\n\tissn = {0169-409X},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0169409X22001284},\n\tdoi = {10.1016/j.addr.2022.114238},\n\tabstract = {Effective delivery of therapeutic and diagnostic nanoparticles is dependent on their ability to accumulate in diseased tissues. However, most nanoparticles end up in liver macrophages regardless of nanoparticle design after administration. In this review, we describe the interactions of liver macrophages with nanoparticles. Liver macrophages have significant advantages in interacting with circulating nanoparticles over most target cells and tissues in the body. We describe these advantages in this article. Understanding these advantages will enable the development of strategies to overcome liver macrophages and deliver nanoparticles to targeted diseased tissues effectively. Ultimately, these approaches will increase the therapeutic efficacy and diagnostic signal of nanoparticles.},\n\tlanguage = {en},\n\turldate = {2022-04-25},\n\tjournal = {Advanced Drug Delivery Reviews},\n\tauthor = {Ngo, Wayne and Ahmed, Sara and Blackadar, Colin and Bussin, Bram and Ji, Qin and Mladjenovic, Stefan M. and Sepahi, Zahra and Chan, Warren C. W.},\n\tmonth = jun,\n\tyear = {2022},\n\tkeywords = {Drug delivery, Liver, Macrophages, Mononuclear-phagocyte system, Nanoparticles},\n\tpages = {114238},\n}\n\n
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\n Effective delivery of therapeutic and diagnostic nanoparticles is dependent on their ability to accumulate in diseased tissues. However, most nanoparticles end up in liver macrophages regardless of nanoparticle design after administration. In this review, we describe the interactions of liver macrophages with nanoparticles. Liver macrophages have significant advantages in interacting with circulating nanoparticles over most target cells and tissues in the body. We describe these advantages in this article. Understanding these advantages will enable the development of strategies to overcome liver macrophages and deliver nanoparticles to targeted diseased tissues effectively. Ultimately, these approaches will increase the therapeutic efficacy and diagnostic signal of nanoparticles.\n
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\n \n\n \n \n \n \n \n \n Impact of Tumor Barriers on Nanoparticle Delivery to Macrophages.\n \n \n \n \n\n\n \n Ouyang, B., Kingston, B. R., Poon, W., Zhang, Y., Lin, Z. P., Syed, A. M., Couture-Senécal, J., & Chan, W. C. W.\n\n\n \n\n\n\n Molecular Pharmaceutics. March 2022.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"ImpactPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{ouyang_impact_2022,\n\ttitle = {Impact of {Tumor} {Barriers} on {Nanoparticle} {Delivery} to {Macrophages}},\n\tissn = {1543-8384},\n\turl = {https://doi.org/10.1021/acs.molpharmaceut.1c00905},\n\tdoi = {10.1021/acs.molpharmaceut.1c00905},\n\tabstract = {The delivery of therapeutic nanoparticles to target cells is critical to their effectiveness. Here we quantified the impact of biological barriers on the delivery of nanoparticles to macrophages in two different tissues. We compared the delivery of gold nanoparticles to macrophages in the liver versus those in the tumor. We found that nanoparticle delivery to macrophages in the tumor was 75\\% less than to macrophages in the liver due to structural barriers. The tumor-associated macrophages took up more nanoparticles than Kupffer cells in the absence of barriers. Our results highlight the impact of biological barriers on nanoparticle delivery to cellular targets.},\n\turldate = {2022-04-25},\n\tjournal = {Molecular Pharmaceutics},\n\tauthor = {Ouyang, Ben and Kingston, Benjamin R. and Poon, Wilson and Zhang, Yi-Nan and Lin, Zachary P. and Syed, Abdullah M. and Couture-Senécal, Julien and Chan, Warren C. W.},\n\tmonth = mar,\n\tyear = {2022},\n\tnote = {Publisher: American Chemical Society},\n}\n\n
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\n The delivery of therapeutic nanoparticles to target cells is critical to their effectiveness. Here we quantified the impact of biological barriers on the delivery of nanoparticles to macrophages in two different tissues. We compared the delivery of gold nanoparticles to macrophages in the liver versus those in the tumor. We found that nanoparticle delivery to macrophages in the tumor was 75% less than to macrophages in the liver due to structural barriers. The tumor-associated macrophages took up more nanoparticles than Kupffer cells in the absence of barriers. Our results highlight the impact of biological barriers on nanoparticle delivery to cellular targets.\n
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\n \n\n \n \n \n \n \n \n The Impact of Patient Characteristics on Diagnostic Test Performance.\n \n \n \n \n\n\n \n Kozlowski, H. N., Sindhwani, S., & Chan, W. C. W.\n\n\n \n\n\n\n Small Methods, n/a(n/a): 2101233. 2022.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/smtd.202101233\n\n\n\n
\n\n\n\n \n \n \"ThePaper\n  \n \n \n \"The paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{kozlowski_impact_nodate,\n\ttitle = {The {Impact} of {Patient} {Characteristics} on {Diagnostic} {Test} {Performance}},\n\tvolume = {n/a},\n\tissn = {2366-9608},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/smtd.202101233},\n\tdoi = {10.1002/smtd.202101233},\n\tabstract = {Diagnostic tests can detect diseases, monitor responses, and inform treatments. They are vital to the effective management of disease. There have been significant advances in the engineering of new diagnostic technologies. These technologies may forgo sample extraction, simplify readout, or automate processing. Many researchers design these diagnostics based on test performance in a limited sample subset. This approach ignores the intertwined relationship between patient characteristics and diagnostic test results. Yet, it is important to understand the clinical decision-making workflow and how the disease manifests in order to optimally design diagnostic tests. This review article explores the three aspects of incorporating patient characteristics to maximize diagnostic performance. 1) Characterize patient populations using patient demographics, disease prevalence, and other unique features. 2) Use the characteristics of the patient population to establish design requirements. 3) Determine the best use case since each case has different performance and target requirements. In this framework the clinical, technological, and unmet needs of a patient population shape the diagnostics design requirements. Following these steps will lead to maximal diagnostic performance and poise new diagnostics for real world use.},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2022-01-10},\n\tjournal = {Small Methods},\n\tauthor = {Kozlowski, Hannah N. and Sindhwani, Shrey and Chan, Warren C. W.},\n\tyear = {2022},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/smtd.202101233},\n\tkeywords = {clinical translation, design requirements, molecular diagnostics, multiplex tests},\n\tpages = {2101233},\n\turl_Paper = https://inbs.med.utoronto.ca/wp-content/uploads/2022/01/Kozlowski-et-al.-The-Impact-of-Patient-Characteristics-on-Diagnosti.pdf\n}\n\n
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\n Diagnostic tests can detect diseases, monitor responses, and inform treatments. They are vital to the effective management of disease. There have been significant advances in the engineering of new diagnostic technologies. These technologies may forgo sample extraction, simplify readout, or automate processing. Many researchers design these diagnostics based on test performance in a limited sample subset. This approach ignores the intertwined relationship between patient characteristics and diagnostic test results. Yet, it is important to understand the clinical decision-making workflow and how the disease manifests in order to optimally design diagnostic tests. This review article explores the three aspects of incorporating patient characteristics to maximize diagnostic performance. 1) Characterize patient populations using patient demographics, disease prevalence, and other unique features. 2) Use the characteristics of the patient population to establish design requirements. 3) Determine the best use case since each case has different performance and target requirements. In this framework the clinical, technological, and unmet needs of a patient population shape the diagnostics design requirements. Following these steps will lead to maximal diagnostic performance and poise new diagnostics for real world use.\n
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\n \n\n \n \n \n \n \n \n Specific Endothelial Cells Govern Nanoparticle Entry into Solid Tumors.\n \n \n \n \n\n\n \n Kingston, B. R., Lin, Z. P., Ouyang, B., MacMillan, P., Ngai, J., Syed, A. M., Sindhwani, S., & Chan, W. C. W.\n\n\n \n\n\n\n ACS Nano, 15(9): 14080–14094. September 2021.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"SpecificPaper\n  \n \n \n \"Specific paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 25 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{kingston_specific_2021,\n\ttitle = {Specific {Endothelial} {Cells} {Govern} {Nanoparticle} {Entry} into {Solid} {Tumors}},\n\tvolume = {15},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.1c04510},\n\tdoi = {10.1021/acsnano.1c04510},\n\tabstract = {The successful delivery of nanoparticles to solid tumors depends on their ability to pass through blood vessels and into the tumor microenvironment. Here, we discovered a subset of tumor endothelial cells that facilitate nanoparticle transport into solid tumors. We named these cells nanoparticle transport endothelial cells (N-TECs). We show that only 21\\% of tumor endothelial cells located on a small number of vessels are involved in transporting nanoparticles into the tumor microenvironment. N-TECs have an increased expression of genes related to nanoparticle transport and vessel permeability compared to other tumor endothelial cells. The N-TECs act as gatekeepers that determine the entry point, distribution, cell accessibility, and number of nanoparticles that enter the tumor microenvironment.},\n\tnumber = {9},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Kingston, Benjamin R. and Lin, Zachary P. and Ouyang, Ben and MacMillan, Presley and Ngai, Jessica and Syed, Abdullah Muhammad and Sindhwani, Shrey and Chan, Warren C. W.},\n\tmonth = sep,\n\tyear = {2021},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {14080--14094},\n\tfile = {Full Text PDF:files/1767/Kingston et al. - 2021 - Specific Endothelial Cells Govern Nanoparticle Ent.pdf:application/pdf;ACS Full Text Snapshot:files/1768/acsnano.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2022/01/KINGST1.pdf}\n}\n\n
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\n The successful delivery of nanoparticles to solid tumors depends on their ability to pass through blood vessels and into the tumor microenvironment. Here, we discovered a subset of tumor endothelial cells that facilitate nanoparticle transport into solid tumors. We named these cells nanoparticle transport endothelial cells (N-TECs). We show that only 21% of tumor endothelial cells located on a small number of vessels are involved in transporting nanoparticles into the tumor microenvironment. N-TECs have an increased expression of genes related to nanoparticle transport and vessel permeability compared to other tumor endothelial cells. The N-TECs act as gatekeepers that determine the entry point, distribution, cell accessibility, and number of nanoparticles that enter the tumor microenvironment.\n
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\n \n\n \n \n \n \n \n \n Surveilling and Tracking COVID-19 Patients Using a Portable Quantum Dot Smartphone Device.\n \n \n \n \n\n\n \n Zhang, Y., Malekjahani, A., Udugama, B. N., Kadhiresan, P., Chen, H., Osborne, M., Franz, M., Kucera, M., Plenderleith, S., Yip, L., Bader, G. D., Tran, V., Gubbay, J. B., McGeer, A., Mubareka, S., & Chan, W. C. W.\n\n\n \n\n\n\n Nano Lett., 21(12): 5209–5216. June 2021.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"SurveillingPaper\n  \n \n \n \"Surveilling paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{zhang_surveilling_2021,\n\ttitle = {Surveilling and {Tracking} {COVID}-19 {Patients} {Using} a {Portable} {Quantum} {Dot} {Smartphone} {Device}},\n\tvolume = {21},\n\tissn = {1530-6984},\n\turl = {https://doi.org/10.1021/acs.nanolett.1c01280},\n\tdoi = {10.1021/acs.nanolett.1c01280},\n\tabstract = {The ability to rapidly diagnose, track, and disseminate information for SARS-CoV-2 is critical to minimize its spread. Here, we engineered a portable smartphone-based quantum barcode serological assay device for real-time surveillance of patients infected with SARS-CoV-2. Our device achieved a clinical sensitivity of 90\\% and specificity of 100\\% for SARS-CoV-2, as compared to 34\\% and 100\\%, respectively, for lateral flow assays in a head-to-head comparison. The lateral flow assay misdiagnosed ∼2 out of 3 SARS-CoV-2 positive patients. Our quantum dot barcode device has ∼3 times greater clinical sensitivity because it is ∼140 times more analytically sensitive than lateral flow assays. Our device can diagnose SARS-CoV-2 at different sampling dates and infectious severity. We developed a databasing app to provide instantaneous results to inform patients, physicians, and public health agencies. This assay and device enable real-time surveillance of SARS-CoV-2 seroprevalence and potential immunity.},\n\tnumber = {12},\n\turldate = {2021-11-06},\n\tjournal = {Nano Lett.},\n\tauthor = {Zhang, Yuwei and Malekjahani, Ayden and Udugama, Buddhisha N. and Kadhiresan, Pranav and Chen, Hongmin and Osborne, Matthew and Franz, Max and Kucera, Mike and Plenderleith, Simon and Yip, Lily and Bader, Gary D. and Tran, Vanessa and Gubbay, Jonathan B. and McGeer, Allison and Mubareka, Samira and Chan, Warren C. W.},\n\tmonth = jun,\n\tyear = {2021},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {5209--5216},\n\tfile = {Full Text PDF:files/1770/Zhang et al. - 2021 - Surveilling and Tracking COVID-19 Patients Using a.pdf:application/pdf;ACS Full Text Snapshot:files/1772/acs.nanolett.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2022/01/Zhang-et-al.-2021-Surveilling-and-Tracking-COVID-19-Patients-Using-a.pdf}\n}\n\n
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\n The ability to rapidly diagnose, track, and disseminate information for SARS-CoV-2 is critical to minimize its spread. Here, we engineered a portable smartphone-based quantum barcode serological assay device for real-time surveillance of patients infected with SARS-CoV-2. Our device achieved a clinical sensitivity of 90% and specificity of 100% for SARS-CoV-2, as compared to 34% and 100%, respectively, for lateral flow assays in a head-to-head comparison. The lateral flow assay misdiagnosed ∼2 out of 3 SARS-CoV-2 positive patients. Our quantum dot barcode device has ∼3 times greater clinical sensitivity because it is ∼140 times more analytically sensitive than lateral flow assays. Our device can diagnose SARS-CoV-2 at different sampling dates and infectious severity. We developed a databasing app to provide instantaneous results to inform patients, physicians, and public health agencies. This assay and device enable real-time surveillance of SARS-CoV-2 seroprevalence and potential immunity.\n
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\n \n\n \n \n \n \n \n \n Diagnosing Antibiotic Resistance Using Nucleic Acid Enzymes and Gold Nanoparticles.\n \n \n \n \n\n\n \n Abdou Mohamed, M. A., Kozlowski, H. N., Kim, J., Zagorovsky, K., Kantor, M., Feld, J. J., Mubareka, S., Mazzulli, T., & Chan, W. C. W.\n\n\n \n\n\n\n ACS Nano, 15(6): 9379–9390. June 2021.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"DiagnosingPaper\n  \n \n \n \"Diagnosing paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 7 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{abdou_mohamed_diagnosing_2021,\n\ttitle = {Diagnosing {Antibiotic} {Resistance} {Using} {Nucleic} {Acid} {Enzymes} and {Gold} {Nanoparticles}},\n\tvolume = {15},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.0c09902},\n\tdoi = {10.1021/acsnano.0c09902},\n\tabstract = {The rapid and accurate detection of antimicrobial resistance is critical to limiting the spread of infections and delivering effective treatments. Here, we developed a rapid, sensitive, and simple colorimetric nanodiagnostic platform to identify disease-causing pathogens and their associated antibiotic resistance genes within 2 h. The platform can detect bacteria from different biological samples (i.e., blood, wound swabs) with or without culturing. We validated the multicomponent nucleic acid enzyme–gold nanoparticle (MNAzyme-GNP) platform by screening patients with central line associated bloodstream infections and achieved a clinical sensitivity and specificity of 86\\% and 100\\%, respectively. We detected antibiotic resistance in methicillin-resistant Staphylococcus aureus (MRSA) in patient swabs with 90\\% clinical sensitivity and 95\\% clinical specificity. Finally, we identified mecA resistance genes in uncultured nasal, groin, axilla, and wound swabs from patients with 90\\% clinical sensitivity and 95\\% clinical specificity. The simplicity and versatility for detecting bacteria and antibiotic resistance markers make our platform attractive for the broad screening of microbial pathogens.},\n\tnumber = {6},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Abdou Mohamed, Mohamed A. and Kozlowski, Hannah N. and Kim, Jisung and Zagorovsky, Kyryl and Kantor, Melinda and Feld, Jordan J. and Mubareka, Samira and Mazzulli, Tony and Chan, Warren C. W.},\n\tmonth = jun,\n\tyear = {2021},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {9379--9390},\n\tfile = {Full Text PDF:files/1773/Abdou Mohamed et al. - 2021 - Diagnosing Antibiotic Resistance Using Nucleic Aci.pdf:application/pdf;ACS Full Text Snapshot:files/1775/acsnano.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2022/01/ABDOUM1.pdf}\n}\n\n
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\n The rapid and accurate detection of antimicrobial resistance is critical to limiting the spread of infections and delivering effective treatments. Here, we developed a rapid, sensitive, and simple colorimetric nanodiagnostic platform to identify disease-causing pathogens and their associated antibiotic resistance genes within 2 h. The platform can detect bacteria from different biological samples (i.e., blood, wound swabs) with or without culturing. We validated the multicomponent nucleic acid enzyme–gold nanoparticle (MNAzyme-GNP) platform by screening patients with central line associated bloodstream infections and achieved a clinical sensitivity and specificity of 86% and 100%, respectively. We detected antibiotic resistance in methicillin-resistant Staphylococcus aureus (MRSA) in patient swabs with 90% clinical sensitivity and 95% clinical specificity. Finally, we identified mecA resistance genes in uncultured nasal, groin, axilla, and wound swabs from patients with 90% clinical sensitivity and 95% clinical specificity. The simplicity and versatility for detecting bacteria and antibiotic resistance markers make our platform attractive for the broad screening of microbial pathogens.\n
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\n \n\n \n \n \n \n \n \n Nanotechnology for modern medicine: next step towards clinical translation.\n \n \n \n \n\n\n \n Sindhwani, S., & Chan, W. C. W.\n\n\n \n\n\n\n Journal of Internal Medicine, 290(3): 486–498. 2021.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/joim.13254\n\n\n\n
\n\n\n\n \n \n \"NanotechnologyPaper\n  \n \n \n \"Nanotechnology paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 8 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n\n\n\n
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@article{sindhwani_nanotechnology_2021,\n\ttitle = {Nanotechnology for modern medicine: next step towards clinical translation},\n\tvolume = {290},\n\tissn = {1365-2796},\n\tshorttitle = {Nanotechnology for modern medicine},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1111/joim.13254},\n\tdoi = {10.1111/joim.13254},\n\tabstract = {The field of nanotechnology has been a significant research focus in the last thirty years. This emphasis is due to the unique optical, electrical, magnetic, chemical and biological properties of materials approximately ten thousand times smaller than the diameter of a hair strand. Researchers have developed methods to synthesize and characterize large libraries of nanomaterials and have demonstrated their preclinical utility. We have entered a new phase of nanomedicine development, where the focus is to translate these technologies to benefit patients. This review article provides an overview of nanomedicine's unique properties, the current state of the field, and discusses the challenge of clinical translation. Finally, we discuss the need to build and strengthen partnerships between engineers and clinicians to create a feedback loop between the bench and bedside. This partnership will guide fundamental studies on the nanoparticle–biological interactions, address clinical challenges and change the development and evaluation of new drug delivery systems, sensors, imaging agents and therapeutic systems.},\n\tlanguage = {en},\n\tnumber = {3},\n\turldate = {2021-11-06},\n\tjournal = {Journal of Internal Medicine},\n\tauthor = {Sindhwani, Shrey and Chan, Warren C. W.},\n\tyear = {2021},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/joim.13254},\n\tkeywords = {cancer, medicine, nanotechnology},\n\tpages = {486--498},\n\tfile = {Full Text PDF:files/1776/Sindhwani and Chan - 2021 - Nanotechnology for modern medicine next step towa.pdf:application/pdf;Snapshot:files/1777/joim.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2022/01/SINDHW1.pdf}\n}\n\n
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\n The field of nanotechnology has been a significant research focus in the last thirty years. This emphasis is due to the unique optical, electrical, magnetic, chemical and biological properties of materials approximately ten thousand times smaller than the diameter of a hair strand. Researchers have developed methods to synthesize and characterize large libraries of nanomaterials and have demonstrated their preclinical utility. We have entered a new phase of nanomedicine development, where the focus is to translate these technologies to benefit patients. This review article provides an overview of nanomedicine's unique properties, the current state of the field, and discusses the challenge of clinical translation. Finally, we discuss the need to build and strengthen partnerships between engineers and clinicians to create a feedback loop between the bench and bedside. This partnership will guide fundamental studies on the nanoparticle–biological interactions, address clinical challenges and change the development and evaluation of new drug delivery systems, sensors, imaging agents and therapeutic systems.\n
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\n \n\n \n \n \n \n \n \n A Colorimetric Test to Differentiate Patients Infected with Influenza from COVID-19.\n \n \n \n \n\n\n \n Kozlowski, H. N., Abdou Mohamed, M. A., Kim, J., Bell, N. G., Zagorovsky, K., Mubareka, S., & Chan, W. C. W.\n\n\n \n\n\n\n Small Structures, 2(8): 2100034. 2021.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/sstr.202100034\n\n\n\n
\n\n\n\n \n \n \"APaper\n  \n \n \n \"A paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{kozlowski_colorimetric_2021,\n\ttitle = {A {Colorimetric} {Test} to {Differentiate} {Patients} {Infected} with {Influenza} from {COVID}-19},\n\tvolume = {2},\n\tissn = {2688-4062},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/sstr.202100034},\n\tdoi = {10.1002/sstr.202100034},\n\tabstract = {Patients infected with SARS-CoV-2 and influenza display similar symptoms, but treatment requirements are different. Clinicians need to accurately distinguish SARS-CoV-2 from influenza to provide appropriate treatment. Here, the authors develope a color-based technique to differentiate between patients infected with SARS-CoV-2 and influenza A using a nucleic acid enzyme-gold nanoparticle (GNP) molecular test requiring minimal equipment. The MNAzyme and GNP probes are designed to be robust to viral mutations. Conserved regions of the viral genomes are targeted, and two MNAzymes are created for each virus. The ability of the system to distinguish between SARS-CoV-2 and influenza A using 79 patient samples is tested. When detecting SARS-CoV-2 positive patients, the clinical sensitivity is 90\\%, and the specificity is 100\\%. When detecting influenza A, the clinical sensitivity and specificity are 93\\% and 100\\%, respectively. The high clinical performance of the MNAzyme-GNP assay shows that it can be used to help clinicians choose effective treatments.},\n\tlanguage = {en},\n\tnumber = {8},\n\turldate = {2021-11-06},\n\tjournal = {Small Structures},\n\tauthor = {Kozlowski, Hannah N. and Abdou Mohamed, Mohamed A. and Kim, Jisung and Bell, Natalie G. and Zagorovsky, Kyryl and Mubareka, Samira and Chan, Warren C. W.},\n\tyear = {2021},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/sstr.202100034},\n\tkeywords = {colorimetric, diagnostics, DNAzymes, gold nanoparticles, influenza A, respiratory infections, SARS-CoV-2},\n\tpages = {2100034},\n\tfile = {Full Text PDF:files/1780/Kozlowski et al. - 2021 - A Colorimetric Test to Differentiate Patients Infe.pdf:application/pdf;Snapshot:files/1781/sstr.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2022/01/KOZLOW1.pdf}\n}\n\n
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\n Patients infected with SARS-CoV-2 and influenza display similar symptoms, but treatment requirements are different. Clinicians need to accurately distinguish SARS-CoV-2 from influenza to provide appropriate treatment. Here, the authors develope a color-based technique to differentiate between patients infected with SARS-CoV-2 and influenza A using a nucleic acid enzyme-gold nanoparticle (GNP) molecular test requiring minimal equipment. The MNAzyme and GNP probes are designed to be robust to viral mutations. Conserved regions of the viral genomes are targeted, and two MNAzymes are created for each virus. The ability of the system to distinguish between SARS-CoV-2 and influenza A using 79 patient samples is tested. When detecting SARS-CoV-2 positive patients, the clinical sensitivity is 90%, and the specificity is 100%. When detecting influenza A, the clinical sensitivity and specificity are 93% and 100%, respectively. The high clinical performance of the MNAzyme-GNP assay shows that it can be used to help clinicians choose effective treatments.\n
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\n \n\n \n \n \n \n \n \n Subtherapeutic Photodynamic Treatment Facilitates Tumor Nanomedicine Delivery and Overcomes Desmoplasia.\n \n \n \n \n\n\n \n Overchuk, M., Harmatys, K. M., Sindhwani, S., Rajora, M. A., Koebel, A., Charron, D. M., Syed, A. M., Chen, J., Pomper, M. G., Wilson, B. C., Chan, W. C. W., & Zheng, G.\n\n\n \n\n\n\n Nano Lett., 21(1): 344–352. January 2021.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"SubtherapeuticPaper\n  \n \n \n \"Subtherapeutic paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{overchuk_subtherapeutic_2021,\n\ttitle = {Subtherapeutic {Photodynamic} {Treatment} {Facilitates} {Tumor} {Nanomedicine} {Delivery} and {Overcomes} {Desmoplasia}},\n\tvolume = {21},\n\tissn = {1530-6984},\n\turl = {https://doi.org/10.1021/acs.nanolett.0c03731},\n\tdoi = {10.1021/acs.nanolett.0c03731},\n\tabstract = {Limited tumor nanoparticle accumulation remains one of the main challenges in cancer nanomedicine. Here, we demonstrate that subtherapeutic photodynamic priming (PDP) enhances the accumulation of nanoparticles in subcutaneous murine prostate tumors ∼3–5-times without inducing cell death, vascular destruction, or tumor growth delay. We also found that PDP resulted in an ∼2-times decrease in tumor collagen content as well as a significant reduction of extracellular matrix density in the subendothelial zone. Enhanced nanoparticle accumulation combined with the reduced extravascular barriers improved therapeutic efficacy in the absence of off-target toxicity, wherein 5 mg/kg of Doxil with PDP was equally effective in delaying tumor growth as 15 mg/kg of Doxil. Overall, this study demonstrates the potential of PDP to enhance tumor nanomedicine accumulation and alleviate tumor desmoplasia without causing cell death or vascular destruction, highlighting the utility of PDP as a minimally invasive priming strategy that can improve therapeutic outcomes in desmoplastic tumors.},\n\tnumber = {1},\n\turldate = {2021-11-06},\n\tjournal = {Nano Lett.},\n\tauthor = {Overchuk, Marta and Harmatys, Kara M. and Sindhwani, Shrey and Rajora, Maneesha A. and Koebel, Adam and Charron, Danielle M. and Syed, Abdullah M. and Chen, Juan and Pomper, Martin G. and Wilson, Brian C. and Chan, Warren C. W. and Zheng, Gang},\n\tmonth = jan,\n\tyear = {2021},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {344--352},\n\tfile = {Full Text PDF:files/1786/Overchuk et al. - 2021 - Subtherapeutic Photodynamic Treatment Facilitates .pdf:application/pdf;ACS Full Text Snapshot:files/1788/acs.nanolett.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2022/01/OVERCH1.pdf}\n}\n\n
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\n Limited tumor nanoparticle accumulation remains one of the main challenges in cancer nanomedicine. Here, we demonstrate that subtherapeutic photodynamic priming (PDP) enhances the accumulation of nanoparticles in subcutaneous murine prostate tumors ∼3–5-times without inducing cell death, vascular destruction, or tumor growth delay. We also found that PDP resulted in an ∼2-times decrease in tumor collagen content as well as a significant reduction of extracellular matrix density in the subendothelial zone. Enhanced nanoparticle accumulation combined with the reduced extravascular barriers improved therapeutic efficacy in the absence of off-target toxicity, wherein 5 mg/kg of Doxil with PDP was equally effective in delaying tumor growth as 15 mg/kg of Doxil. Overall, this study demonstrates the potential of PDP to enhance tumor nanomedicine accumulation and alleviate tumor desmoplasia without causing cell death or vascular destruction, highlighting the utility of PDP as a minimally invasive priming strategy that can improve therapeutic outcomes in desmoplastic tumors.\n
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\n \n\n \n \n \n \n \n \n Growing Contributions of Nano in 2020.\n \n \n \n \n\n\n \n Brinker, C. J., Buriak, J. M., Chan, W. C. W., Chhowalla, M., Glotzer, S. C., Gogotsi, Y., Hammond, P. T., Hersam, M. C., Javey, A., Kagan, C. R., Kataoka, K., Khademhosseini, A., Kim, I., Kotov, N. A., Lee, S., Lee, Y. H., Li, Y., Liz-Marzán, L. M., Millstone, J. E., Mulvaney, P., Nel, A. E., Nordlander, P., Parak, W. J., Penner, R. M., Rogach, A. L., Schaak, R. E., Sood, A. K., Stevens, M. M., Wee, A. T. S., Weil, T., Wilson, C. G., & Weiss, P. S.\n\n\n \n\n\n\n ACS Nano, 14(12): 16163–16164. December 2020.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"GrowingPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n  \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{brinker_growing_2020,\n\ttitle = {Growing {Contributions} of {Nano} in 2020},\n\tvolume = {14},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.0c10429},\n\tdoi = {10.1021/acsnano.0c10429},\n\tnumber = {12},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Brinker, C. Jeffrey and Buriak, Jillian M. and Chan, Warren C. W. and Chhowalla, Manish and Glotzer, Sharon C. and Gogotsi, Yury and Hammond, Paula T. and Hersam, Mark C. and Javey, Ali and Kagan, Cherie R. and Kataoka, Kazunori and Khademhosseini, Ali and Kim, Il-Doo and Kotov, Nicholas A. and Lee, Shuit-Tong and Lee, Young Hee and Li, Yan and Liz-Marzán, Luis M. and Millstone, Jill E. and Mulvaney, Paul and Nel, Andre E. and Nordlander, Peter and Parak, Wolfgang J. and Penner, Reginald M. and Rogach, Andrey L. and Schaak, Raymond E. and Sood, A. K. and Stevens, Molly M. and Wee, Andrew T. S. and Weil, Tanja and Wilson, C. Grant and Weiss, Paul S.},\n\tmonth = dec,\n\tyear = {2020},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {16163--16164},\n\tfile = {Full Text PDF:files/1783/Brinker et al. - 2020 - Growing Contributions of Nano in 2020.pdf:application/pdf;ACS Full Text Snapshot:files/1784/acsnano.html:text/html},\n}\n\n
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\n \n\n \n \n \n \n \n \n The dose threshold for nanoparticle tumour delivery.\n \n \n \n \n\n\n \n Ouyang, B., Poon, W., Zhang, Y., Lin, Z. P., Kingston, B. R., Tavares, A. J., Zhang, Y., Chen, J., Valic, M. S., Syed, A. M., MacMillan, P., Couture-Senécal, J., Zheng, G., & Chan, W. C. W.\n\n\n \n\n\n\n Nat. Mater., 19(12): 1362–1371. December 2020.\n Bandiera_abtest: a Cg_type: Nature Research Journals Number: 12 Primary_atype: Research Publisher: Nature Publishing Group Subject_term: Cancer therapy;Nanoparticles Subject_term_id: cancer-therapy;nanoparticles\n\n\n\n
\n\n\n\n \n \n \"ThePaper\n  \n \n \n \"The paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 17 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n\n\n\n
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@article{ouyang_dose_2020,\n\ttitle = {The dose threshold for nanoparticle tumour delivery},\n\tvolume = {19},\n\tcopyright = {2020 The Author(s), under exclusive licence to Springer Nature Limited},\n\tissn = {1476-4660},\n\turl = {https://www.nature.com/articles/s41563-020-0755-z},\n\tdoi = {10.1038/s41563-020-0755-z},\n\tabstract = {Nanoparticle delivery to solid tumours over the past ten years has stagnated at a median of 0.7\\% of the injected dose. Varying nanoparticle designs and strategies have yielded only minor improvements. Here we discovered a dose threshold for improving nanoparticle tumour delivery: 1 trillion nanoparticles in mice. Doses above this threshold overwhelmed Kupffer cell uptake rates, nonlinearly decreased liver clearance, prolonged circulation and increased nanoparticle tumour delivery. This enabled up to 12\\% tumour delivery efficiency and delivery to 93\\% of cells in tumours, and also improved the therapeutic efficacy of Caelyx/Doxil. This threshold was robust across different nanoparticle types, tumour models and studies across ten years of the literature. Our results have implications for human translation and highlight a simple, but powerful, principle for designing nanoparticle cancer treatments.},\n\tlanguage = {en},\n\tnumber = {12},\n\turldate = {2021-11-06},\n\tjournal = {Nat. Mater.},\n\tauthor = {Ouyang, Ben and Poon, Wilson and Zhang, Yi-Nan and Lin, Zachary P. and Kingston, Benjamin R. and Tavares, Anthony J. and Zhang, Yuwei and Chen, Juan and Valic, Michael S. and Syed, Abdullah M. and MacMillan, Presley and Couture-Senécal, Julien and Zheng, Gang and Chan, Warren C. W.},\n\tmonth = dec,\n\tyear = {2020},\n\tnote = {Bandiera\\_abtest: a\nCg\\_type: Nature Research Journals\nNumber: 12\nPrimary\\_atype: Research\nPublisher: Nature Publishing Group\nSubject\\_term: Cancer therapy;Nanoparticles\nSubject\\_term\\_id: cancer-therapy;nanoparticles},\n\tkeywords = {Cancer therapy, Nanoparticles},\n\tpages = {1362--1371},\n\tfile = {Full Text PDF:files/1789/Ouyang et al. - 2020 - The dose threshold for nanoparticle tumour deliver.pdf:application/pdf;Snapshot:files/1790/s41563-020-0755-z.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2022/01/Ouyang-et-al.-2020-The-dose-threshold-for-nanoparticle-tumour-deliver.pdf}\n}\n\n
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\n Nanoparticle delivery to solid tumours over the past ten years has stagnated at a median of 0.7% of the injected dose. Varying nanoparticle designs and strategies have yielded only minor improvements. Here we discovered a dose threshold for improving nanoparticle tumour delivery: 1 trillion nanoparticles in mice. Doses above this threshold overwhelmed Kupffer cell uptake rates, nonlinearly decreased liver clearance, prolonged circulation and increased nanoparticle tumour delivery. This enabled up to 12% tumour delivery efficiency and delivery to 93% of cells in tumours, and also improved the therapeutic efficacy of Caelyx/Doxil. This threshold was robust across different nanoparticle types, tumour models and studies across ten years of the literature. Our results have implications for human translation and highlight a simple, but powerful, principle for designing nanoparticle cancer treatments.\n
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\n \n\n \n \n \n \n \n \n DNA-Controlled Encapsulation of Small Molecules in Protein Nanoparticles.\n \n \n \n \n\n\n \n Ngo, W., Stordy, B., Lazarovits, J., Raja, E. K., Etienne, C. L., & Chan, W. C. W.\n\n\n \n\n\n\n J. Am. Chem. Soc., 142(42): 17938–17943. October 2020.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"DNA-ControlledPaper\n  \n \n \n \"DNA-Controlled paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 9 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{ngo_dna-controlled_2020,\n\ttitle = {{DNA}-{Controlled} {Encapsulation} of {Small} {Molecules} in {Protein} {Nanoparticles}},\n\tvolume = {142},\n\tissn = {0002-7863},\n\turl = {https://doi.org/10.1021/jacs.0c09914},\n\tdoi = {10.1021/jacs.0c09914},\n\tabstract = {A nanoparticle can hold multiple types of therapeutic and imaging agents for disease treatment and diagnosis. However, controlling the storage of molecules in nanoparticles is challenging, because nonspecific intermolecular interactions are used for encapsulation. Here, we used specific DNA interactions to store molecules in nanoparticles. We made nanoparticles containing DNA anchors to capture DNA-conjugated small molecules. By changing the sequences and stoichiometry of DNA anchors, we can control the amount and ratio of molecules with different chemical properties in the nanoparticles. We modified the cytotoxicity of our nanoparticles to cancer cells by changing the ratio of encapsulated drugs (mertansine and doxorubicin). Specifically controlling the storage of multiple types of molecules allows us to optimize the properties of combination drug and imaging nanoparticles.},\n\tnumber = {42},\n\turldate = {2021-11-06},\n\tjournal = {J. Am. Chem. Soc.},\n\tauthor = {Ngo, Wayne and Stordy, Benjamin and Lazarovits, James and Raja, Erum K. and Etienne, Chris L. and Chan, Warren C. W.},\n\tmonth = oct,\n\tyear = {2020},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {17938--17943},\n\tfile = {Full Text PDF:files/1792/Ngo et al. - 2020 - DNA-Controlled Encapsulation of Small Molecules in.pdf:application/pdf;ACS Full Text Snapshot:files/1793/jacs.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2022/01/Ngo-et-al.-2020-DNA-Controlled-Encapsulation-of-Small-Molecules-in.pdf}\n}\n\n
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\n A nanoparticle can hold multiple types of therapeutic and imaging agents for disease treatment and diagnosis. However, controlling the storage of molecules in nanoparticles is challenging, because nonspecific intermolecular interactions are used for encapsulation. Here, we used specific DNA interactions to store molecules in nanoparticles. We made nanoparticles containing DNA anchors to capture DNA-conjugated small molecules. By changing the sequences and stoichiometry of DNA anchors, we can control the amount and ratio of molecules with different chemical properties in the nanoparticles. We modified the cytotoxicity of our nanoparticles to cancer cells by changing the ratio of encapsulated drugs (mertansine and doxorubicin). Specifically controlling the storage of multiple types of molecules allows us to optimize the properties of combination drug and imaging nanoparticles.\n
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\n \n\n \n \n \n \n \n \n A framework for designing delivery systems.\n \n \n \n \n\n\n \n Poon, W., Kingston, B. R., Ouyang, B., Ngo, W., & Chan, W. C. W.\n\n\n \n\n\n\n Nat. Nanotechnol., 15(10): 819–829. October 2020.\n Bandiera_abtest: a Cg_type: Nature Research Journals Number: 10 Primary_atype: Reviews Publisher: Nature Publishing Group Subject_term: Biomedical engineering;Nanobiotechnology;Nanomedicine;Nanoscale materials Subject_term_id: biomedical-engineering;nanobiotechnology;nanomedicine;nanoscale-materials\n\n\n\n
\n\n\n\n \n \n \"APaper\n  \n \n \n \"A paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 5 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{poon_framework_2020,\n\ttitle = {A framework for designing delivery systems},\n\tvolume = {15},\n\tcopyright = {2020 Springer Nature Limited},\n\tissn = {1748-3395},\n\turl = {https://www.nature.com/articles/s41565-020-0759-5},\n\tdoi = {10.1038/s41565-020-0759-5},\n\tabstract = {The delivery of medical agents to a specific diseased tissue or cell is critical for diagnosing and treating patients. Nanomaterials are promising vehicles to transport agents that include drugs, contrast agents, immunotherapies and gene editors. They can be engineered to have different physical and chemical properties that influence their interactions with their biological environments and delivery destinations. In this Review Article, we discuss nanoparticle delivery systems and how the biology of disease should inform their design. We propose developing a framework for building optimal delivery systems that uses nanoparticle–biological interaction data and computational analyses to guide future nanomaterial designs and delivery strategies.},\n\tlanguage = {en},\n\tnumber = {10},\n\turldate = {2021-11-06},\n\tjournal = {Nat. Nanotechnol.},\n\tauthor = {Poon, Wilson and Kingston, Benjamin R. and Ouyang, Ben and Ngo, Wayne and Chan, Warren C. W.},\n\tmonth = oct,\n\tyear = {2020},\n\tnote = {Bandiera\\_abtest: a\nCg\\_type: Nature Research Journals\nNumber: 10\nPrimary\\_atype: Reviews\nPublisher: Nature Publishing Group\nSubject\\_term: Biomedical engineering;Nanobiotechnology;Nanomedicine;Nanoscale materials\nSubject\\_term\\_id: biomedical-engineering;nanobiotechnology;nanomedicine;nanoscale-materials},\n\tkeywords = {Biomedical engineering, Nanobiotechnology, Nanomedicine, Nanoscale materials},\n\tpages = {819--829},\n\tfile = {Full Text PDF:files/1795/Poon et al. - 2020 - A framework for designing delivery systems.pdf:application/pdf;Snapshot:files/1796/s41565-020-0759-5.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2022/01/Poon-et-al.-2020-A-framework-for-designing-delivery-systems.pdf}\n}\n\n
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\n The delivery of medical agents to a specific diseased tissue or cell is critical for diagnosing and treating patients. Nanomaterials are promising vehicles to transport agents that include drugs, contrast agents, immunotherapies and gene editors. They can be engineered to have different physical and chemical properties that influence their interactions with their biological environments and delivery destinations. In this Review Article, we discuss nanoparticle delivery systems and how the biology of disease should inform their design. We propose developing a framework for building optimal delivery systems that uses nanoparticle–biological interaction data and computational analyses to guide future nanomaterial designs and delivery strategies.\n
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\n \n\n \n \n \n \n \n \n Suppressing Subcapsular Sinus Macrophages Enhances Transport of Nanovaccines to Lymph Node Follicles for Robust Humoral Immunity.\n \n \n \n \n\n\n \n Zhang, Y., Poon, W., Sefton, E., & Chan, W. C.\n\n\n \n\n\n\n ACS Nano, 14(8): 9478–9490. August 2020.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"SuppressingPaper\n  \n \n \n \"Suppressing paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{zhang_suppressing_2020,\n\ttitle = {Suppressing {Subcapsular} {Sinus} {Macrophages} {Enhances} {Transport} of {Nanovaccines} to {Lymph} {Node} {Follicles} for {Robust} {Humoral} {Immunity}},\n\tvolume = {14},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.0c02240},\n\tdoi = {10.1021/acsnano.0c02240},\n\tabstract = {Nanovaccines need to be transported to lymph node follicles to induce humoral immunity and generate neutralizing antibodies. Here, we discovered that subcapsular sinus macrophages play a barrier role to prevent nanovaccines from accessing lymph node follicles. This is illustrated by measuring the humoral immune responses after removing or functionally altering these cells in the nanovaccine transport process. We achieved up to 60 times more antigen-specific antibody production after suppressing subcapsular sinus macrophages. The degree of the enhanced antibody production is dependent on the nanovaccine dose and size, formulation, and administration time. We further found that pharmacological agents that disrupt the macrophage uptake function can be considered as adjuvants in vaccine development. Immunizing mice using nanovaccines formulated with these agents can induce more than 30 times higher antigen-specific antibody production compared to nanovaccines alone. These findings suggest that altering transport barriers to enable more of the nanovaccine to be delivered to the lymph node follicles for neutralizing antibody production is an effective strategy to boost vaccination.},\n\tnumber = {8},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Zhang, Yi-Nan and Poon, Wilson and Sefton, Elana and Chan, Warren C.W.},\n\tmonth = aug,\n\tyear = {2020},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {9478--9490},\n\tfile = {Full Text PDF:files/1798/Zhang et al. - 2020 - Suppressing Subcapsular Sinus Macrophages Enhances.pdf:application/pdf;ACS Full Text Snapshot:files/1799/acsnano.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acsnano.0c02240-min.pdf}\n}\n\n
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\n Nanovaccines need to be transported to lymph node follicles to induce humoral immunity and generate neutralizing antibodies. Here, we discovered that subcapsular sinus macrophages play a barrier role to prevent nanovaccines from accessing lymph node follicles. This is illustrated by measuring the humoral immune responses after removing or functionally altering these cells in the nanovaccine transport process. We achieved up to 60 times more antigen-specific antibody production after suppressing subcapsular sinus macrophages. The degree of the enhanced antibody production is dependent on the nanovaccine dose and size, formulation, and administration time. We further found that pharmacological agents that disrupt the macrophage uptake function can be considered as adjuvants in vaccine development. Immunizing mice using nanovaccines formulated with these agents can induce more than 30 times higher antigen-specific antibody production compared to nanovaccines alone. These findings suggest that altering transport barriers to enable more of the nanovaccine to be delivered to the lymph node follicles for neutralizing antibody production is an effective strategy to boost vaccination.\n
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\n \n\n \n \n \n \n \n \n Flow Rate Affects Nanoparticle Uptake into Endothelial Cells.\n \n \n \n \n\n\n \n Chen, Y. Y., Syed, A. M., MacMillan, P., Rocheleau, J. V., & Chan, W. C. W.\n\n\n \n\n\n\n Advanced Materials, 32(24): 1906274. 2020.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.201906274\n\n\n\n
\n\n\n\n \n \n \"FlowPaper\n  \n \n \n \"Flow paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{chen_flow_2020,\n\ttitle = {Flow {Rate} {Affects} {Nanoparticle} {Uptake} into {Endothelial} {Cells}},\n\tvolume = {32},\n\tissn = {1521-4095},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/adma.201906274},\n\tdoi = {10.1002/adma.201906274},\n\tabstract = {Nanoparticles are commonly administered through systemic injection, which exposes them to the dynamic environment of the bloodstream. Injected nanoparticles travel within the blood and experience a wide range of flow velocities that induce varying shear rates to the blood vessels. Endothelial cells line these vessels, and have been shown to uptake nanoparticles during circulation, but it is difficult to characterize the flow-dependence of this interaction in vivo. Here, a microfluidic system is developed to control the flow rates of nanoparticles as they interact with endothelial cells. Gold nanoparticle uptake into endothelial cells is quantified at varying flow rates, and it is found that increased flow rates lead to decreased nanoparticle uptake. Endothelial cells respond to increased flow shear with decreased ability to uptake the nanoparticles. If cells are sheared the same way, nanoparticle uptake decreases as their flow velocity increases. Modifying nanoparticle surfaces with endothelial-cell-binding ligands partially restores uptake to nonflow levels, suggesting that functionalizing nanoparticles to bind to endothelial cells enables nanoparticles to resist flow effects. In the future, this microfluidic system can be used to test other nanoparticle–endothelial cell interactions under flow. The results of these studies can guide the engineering of nanoparticles for in vivo medical applications.},\n\tlanguage = {en},\n\tnumber = {24},\n\turldate = {2021-11-06},\n\tjournal = {Advanced Materials},\n\tauthor = {Chen, Yih Yang and Syed, Abdullah Muhammad and MacMillan, Presley and Rocheleau, Jonathan V. and Chan, Warren C. W.},\n\tyear = {2020},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.201906274},\n\tkeywords = {blood vessels, flow shear, flow velocity, microfluidics, nanomedicine, nanoparticles},\n\tpages = {1906274},\n\tfile = {Full Text PDF:files/1801/Chen et al. - 2020 - Flow Rate Affects Nanoparticle Uptake into Endothe.pdf:application/pdf;Snapshot:files/1802/adma.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/adma.201906274-min.pdf}\n}\n\n
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\n Nanoparticles are commonly administered through systemic injection, which exposes them to the dynamic environment of the bloodstream. Injected nanoparticles travel within the blood and experience a wide range of flow velocities that induce varying shear rates to the blood vessels. Endothelial cells line these vessels, and have been shown to uptake nanoparticles during circulation, but it is difficult to characterize the flow-dependence of this interaction in vivo. Here, a microfluidic system is developed to control the flow rates of nanoparticles as they interact with endothelial cells. Gold nanoparticle uptake into endothelial cells is quantified at varying flow rates, and it is found that increased flow rates lead to decreased nanoparticle uptake. Endothelial cells respond to increased flow shear with decreased ability to uptake the nanoparticles. If cells are sheared the same way, nanoparticle uptake decreases as their flow velocity increases. Modifying nanoparticle surfaces with endothelial-cell-binding ligands partially restores uptake to nonflow levels, suggesting that functionalizing nanoparticles to bind to endothelial cells enables nanoparticles to resist flow effects. In the future, this microfluidic system can be used to test other nanoparticle–endothelial cell interactions under flow. The results of these studies can guide the engineering of nanoparticles for in vivo medical applications.\n
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\n \n\n \n \n \n \n \n \n Transcribing In Vivo Blood Vessel Networks into In Vitro Perfusable Microfluidic Devices.\n \n \n \n \n\n\n \n Chen, Y. Y., Kingston, B. R., & Chan, W. C. W.\n\n\n \n\n\n\n Advanced Materials Technologies, 5(6): 2000103. 2020.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/admt.202000103\n\n\n\n
\n\n\n\n \n \n \"TranscribingPaper\n  \n \n \n \"Transcribing paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{chen_transcribing_2020,\n\ttitle = {Transcribing {In} {Vivo} {Blood} {Vessel} {Networks} into {In} {Vitro} {Perfusable} {Microfluidic} {Devices}},\n\tvolume = {5},\n\tissn = {2365-709X},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/admt.202000103},\n\tdoi = {10.1002/admt.202000103},\n\tabstract = {The 3D architecture of blood vessel networks dictates how nutrients, waste, and drugs are transported. These transport processes are difficult to study in vivo, leading researchers to develop methods to construct vessel networks in vitro. However, existing methods require expensive, customized equipment and cannot create large ({\\textgreater}1 cm3) constructs. This makes them inaccessible to many researchers or educators. Here, a method that transcribes 3D images of blood vessel networks into physical microfluidic devices is developed. The method takes 3D images of blood vessel networks and uses fused-filament 3D fabrication with standard polylactic acid (PLA) filament to print the imaged vessel network. The 3D printout is cast in polydimethylsiloxane (PDMS) and dissolved, producing vessel channels that are lined with endothelial cells. Devices imprinted with different vessel networks including small intestinal villi, pancreatic islets, and tumors from mice and humans are created. The method replicates the complex geometries of blood vessel networks in an in vitro device with commonly available equipment and materials. This increases the accessibility of this technology by allowing researchers or educators without access to expensive laser ablation microscope set-ups or custom 3D printers to be able to create vasculature network devices.},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2021-11-06},\n\tjournal = {Advanced Materials Technologies},\n\tauthor = {Chen, Yih Yang and Kingston, Benjamin R. and Chan, Warren C. W.},\n\tyear = {2020},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/admt.202000103},\n\tkeywords = {3D printing, blood vessels, microfluidics, tissue engineering},\n\tpages = {2000103},\n\tfile = {Full Text PDF:files/1804/Chen et al. - 2020 - Transcribing In Vivo Blood Vessel Networks into In.pdf:application/pdf},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/admt.202000103-min.pdf}\n}\n\n
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\n The 3D architecture of blood vessel networks dictates how nutrients, waste, and drugs are transported. These transport processes are difficult to study in vivo, leading researchers to develop methods to construct vessel networks in vitro. However, existing methods require expensive, customized equipment and cannot create large (\\textgreater1 cm3) constructs. This makes them inaccessible to many researchers or educators. Here, a method that transcribes 3D images of blood vessel networks into physical microfluidic devices is developed. The method takes 3D images of blood vessel networks and uses fused-filament 3D fabrication with standard polylactic acid (PLA) filament to print the imaged vessel network. The 3D printout is cast in polydimethylsiloxane (PDMS) and dissolved, producing vessel channels that are lined with endothelial cells. Devices imprinted with different vessel networks including small intestinal villi, pancreatic islets, and tumors from mice and humans are created. The method replicates the complex geometries of blood vessel networks in an in vitro device with commonly available equipment and materials. This increases the accessibility of this technology by allowing researchers or educators without access to expensive laser ablation microscope set-ups or custom 3D printers to be able to create vasculature network devices.\n
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\n \n\n \n \n \n \n \n \n The entry of nanoparticles into solid tumours.\n \n \n \n \n\n\n \n Sindhwani, S., Syed, A. M., Ngai, J., Kingston, B. R., Maiorino, L., Rothschild, J., MacMillan, P., Zhang, Y., Rajesh, N. U., Hoang, T., Wu, J. L. Y., Wilhelm, S., Zilman, A., Gadde, S., Sulaiman, A., Ouyang, B., Lin, Z., Wang, L., Egeblad, M., & Chan, W. C. W.\n\n\n \n\n\n\n Nat. Mater., 19(5): 566–575. May 2020.\n Bandiera_abtest: a Cg_type: Nature Research Journals Number: 5 Primary_atype: Research Publisher: Nature Publishing Group Subject_term: Cancer microenvironment;Imaging techniques;Nanoparticles;Nanotechnology in cancer Subject_term_id: cancer-microenvironment;imaging-techniques;nanoparticles;nanotechnology-in-cancer\n\n\n\n
\n\n\n\n \n \n \"ThePaper\n  \n \n \n \"The paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 11 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{sindhwani_entry_2020,\n\ttitle = {The entry of nanoparticles into solid tumours},\n\tvolume = {19},\n\tcopyright = {2020 The Author(s), under exclusive licence to Springer Nature Limited},\n\tissn = {1476-4660},\n\turl = {https://www.nature.com/articles/s41563-019-0566-2},\n\tdoi = {10.1038/s41563-019-0566-2},\n\tabstract = {The concept of nanoparticle transport through gaps between endothelial cells (inter-endothelial gaps) in the tumour blood vessel is a central paradigm in cancer nanomedicine. The size of these gaps was found to be up to 2,000 nm. This justified the development of nanoparticles to treat solid tumours as their size is small enough to extravasate and access the tumour microenvironment. Here we show that these inter-endothelial gaps are not responsible for the transport of nanoparticles into solid tumours. Instead, we found that up to 97\\% of nanoparticles enter tumours using an active process through endothelial cells. This result is derived from analysis of four different mouse models, three different types of human tumours, mathematical simulation and modelling, and two different types of imaging techniques. These results challenge our current rationale for developing cancer nanomedicine and suggest that understanding these active pathways will unlock strategies to enhance tumour accumulation.},\n\tlanguage = {en},\n\tnumber = {5},\n\turldate = {2021-11-06},\n\tjournal = {Nat. Mater.},\n\tauthor = {Sindhwani, Shrey and Syed, Abdullah Muhammad and Ngai, Jessica and Kingston, Benjamin R. and Maiorino, Laura and Rothschild, Jeremy and MacMillan, Presley and Zhang, Yuwei and Rajesh, Netra Unni and Hoang, Tran and Wu, Jamie L. Y. and Wilhelm, Stefan and Zilman, Anton and Gadde, Suresh and Sulaiman, Andrew and Ouyang, Ben and Lin, Zachary and Wang, Lisheng and Egeblad, Mikala and Chan, Warren C. W.},\n\tmonth = may,\n\tyear = {2020},\n\tnote = {Bandiera\\_abtest: a\nCg\\_type: Nature Research Journals\nNumber: 5\nPrimary\\_atype: Research\nPublisher: Nature Publishing Group\nSubject\\_term: Cancer microenvironment;Imaging techniques;Nanoparticles;Nanotechnology in cancer\nSubject\\_term\\_id: cancer-microenvironment;imaging-techniques;nanoparticles;nanotechnology-in-cancer},\n\tkeywords = {Cancer microenvironment, Imaging techniques, Nanoparticles, Nanotechnology in cancer},\n\tpages = {566--575},\n\tfile = {Full Text PDF:files/1806/Sindhwani et al. - 2020 - The entry of nanoparticles into solid tumours.pdf:application/pdf;Snapshot:files/1808/s41563-019-0566-2.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2022/01/Sindhwani-et-al.-2020-The-entry-of-nanoparticles-into-solid-tumours.pdf}\n}\n\n
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\n The concept of nanoparticle transport through gaps between endothelial cells (inter-endothelial gaps) in the tumour blood vessel is a central paradigm in cancer nanomedicine. The size of these gaps was found to be up to 2,000 nm. This justified the development of nanoparticles to treat solid tumours as their size is small enough to extravasate and access the tumour microenvironment. Here we show that these inter-endothelial gaps are not responsible for the transport of nanoparticles into solid tumours. Instead, we found that up to 97% of nanoparticles enter tumours using an active process through endothelial cells. This result is derived from analysis of four different mouse models, three different types of human tumours, mathematical simulation and modelling, and two different types of imaging techniques. These results challenge our current rationale for developing cancer nanomedicine and suggest that understanding these active pathways will unlock strategies to enhance tumour accumulation.\n
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\n \n\n \n \n \n \n \n \n An Analysis of the Binding Function and Structural Organization of the Protein Corona.\n \n \n \n \n\n\n \n Zhang, Y., Wu, J. L. Y., Lazarovits, J., & Chan, W. C. W.\n\n\n \n\n\n\n J. Am. Chem. Soc., 142(19): 8827–8836. May 2020.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"AnPaper\n  \n \n \n \"An paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{zhang_analysis_2020,\n\ttitle = {An {Analysis} of the {Binding} {Function} and {Structural} {Organization} of the {Protein} {Corona}},\n\tvolume = {142},\n\tissn = {0002-7863},\n\turl = {https://doi.org/10.1021/jacs.0c01853},\n\tdoi = {10.1021/jacs.0c01853},\n\tabstract = {Blood proteins adsorb onto the surface of nanoparticles after intravenous injection to form a protein corona. The underlying organization and binding function of these adsorbed proteins remain unclear. This can impact how the corona mediates cell and tissue interactions. Here, we investigated the function and structural organization of the protein corona using an immunoassay approach. We discovered that only 27\\% of the adsorbed proteins examined are functional for binding to their target protein. This is because the corona architecture is not a monolayer, but an assembly of proteins that are bound to each other. We further demonstrated that we can control the binding functionality of a protein by changing the organization of proteins in the assembly. We show that manipulation of the corona protein composition and assembly can influence their interactions with macrophage cells in culture. This study provides detailed functional and structural insights into the protein corona on nanomaterials and offers a new strategy to manipulate it for controlled interactions with the biological system.},\n\tnumber = {19},\n\turldate = {2021-11-06},\n\tjournal = {J. Am. Chem. Soc.},\n\tauthor = {Zhang, Yuwei and Wu, Jamie L. Y. and Lazarovits, James and Chan, Warren C. W.},\n\tmonth = may,\n\tyear = {2020},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {8827--8836},\n\tfile = {Full Text PDF:files/1810/Zhang et al. - 2020 - An Analysis of the Binding Function and Structural.pdf:application/pdf;ACS Full Text Snapshot:files/1818/jacs.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/jacs.0c01853-min.pdf}\n}\n\n
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\n Blood proteins adsorb onto the surface of nanoparticles after intravenous injection to form a protein corona. The underlying organization and binding function of these adsorbed proteins remain unclear. This can impact how the corona mediates cell and tissue interactions. Here, we investigated the function and structural organization of the protein corona using an immunoassay approach. We discovered that only 27% of the adsorbed proteins examined are functional for binding to their target protein. This is because the corona architecture is not a monolayer, but an assembly of proteins that are bound to each other. We further demonstrated that we can control the binding functionality of a protein by changing the organization of proteins in the assembly. We show that manipulation of the corona protein composition and assembly can influence their interactions with macrophage cells in culture. This study provides detailed functional and structural insights into the protein corona on nanomaterials and offers a new strategy to manipulate it for controlled interactions with the biological system.\n
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\n \n\n \n \n \n \n \n \n Nanoparticle Uptake in a Spontaneous and Immunocompetent Woodchuck Liver Cancer Model.\n \n \n \n \n\n\n \n Liu, L. Y., Ma, X., Ouyang, B., Ings, D. P., Marwah, S., Liu, J., Chen, A. Y., Gupta, R., Manuel, J., Chen, X., Gage, B. K., Cirlan, I., Khuu, N., Chung, S., Camat, D., Cheng, M., Sekhon, M., Zagorovsky, K., Abdou Mohamed, M. A., Thoeni, C., Atif, J., Echeverri, J., Kollmann, D., Fischer, S., Bader, G. D., Chan, W. C. W., Michalak, T. I., McGilvray, I. D., & MacParland, S. A.\n\n\n \n\n\n\n ACS Nano, 14(4): 4698–4715. April 2020.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"NanoparticlePaper\n  \n \n \n \"Nanoparticle paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{liu_nanoparticle_2020,\n\ttitle = {Nanoparticle {Uptake} in a {Spontaneous} and {Immunocompetent} {Woodchuck} {Liver} {Cancer} {Model}},\n\tvolume = {14},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.0c00468},\n\tdoi = {10.1021/acsnano.0c00468},\n\tabstract = {There is a tremendous focus on the application of nanomaterials for the treatment of cancer. Nonprimate models are conventionally used to assess the biomedical utility of nanomaterials. However, these animals often lack an intact immunological background, and the tumors in these animals do not develop spontaneously. We introduce a preclinical woodchuck hepatitis virus-induced liver cancer model as a platform for nanoparticle (NP)-based in vivo experiments. Liver cancer development in these out-bred animals occurs as a result of persistent viral infection, mimicking human hepatitis B virus-induced HCC development. We highlight how this model addresses key gaps associated with other commonly used tumor models. We employed this model to (1) track organ biodistribution of gold NPs after intravenous administration, (2) examine their subcellular localization in the liver, (3) determine clearance kinetics, and (4) characterize the identity of hepatic macrophages that take up NPs using RNA-sequencing (RNA-seq). We found that the liver and spleen were the primary sites of NP accumulation. Subcellular analyses revealed accumulation of NPs in the lysosomes of CD14+ cells. Through RNA-seq, we uncovered that immunosuppressive macrophages within the woodchuck liver are the major cell type that take up injected NPs. The woodchuck-HCC model has the potential to be an invaluable tool to examine NP-based immune modifiers that promote host anti-tumor immunity.},\n\tnumber = {4},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Liu, Lewis Y. and Ma, Xue-Zhong and Ouyang, Ben and Ings, Danielle P. and Marwah, Sagar and Liu, Jeff and Chen, Annie Y. and Gupta, Rahul and Manuel, Justin and Chen, Xu-Chun and Gage, Blair K. and Cirlan, Iulia and Khuu, Nicholas and Chung, Sai and Camat, Damra and Cheng, Michael and Sekhon, Manmeet and Zagorovsky, Kyryl and Abdou Mohamed, Mohamed A. and Thoeni, Cornelia and Atif, Jawairia and Echeverri, Juan and Kollmann, Dagmar and Fischer, Sandra and Bader, Gary D. and Chan, Warren C. W. and Michalak, Tomasz I. and McGilvray, Ian D. and MacParland, Sonya A.},\n\tmonth = apr,\n\tyear = {2020},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {4698--4715},\n\tfile = {Full Text PDF:files/1814/Liu et al. - 2020 - Nanoparticle Uptake in a Spontaneous and Immunocom.pdf:application/pdf;ACS Full Text Snapshot:files/1819/acsnano.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acsnano.0c00468-min.pdf}\n}\n\n
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\n\n\n
\n There is a tremendous focus on the application of nanomaterials for the treatment of cancer. Nonprimate models are conventionally used to assess the biomedical utility of nanomaterials. However, these animals often lack an intact immunological background, and the tumors in these animals do not develop spontaneously. We introduce a preclinical woodchuck hepatitis virus-induced liver cancer model as a platform for nanoparticle (NP)-based in vivo experiments. Liver cancer development in these out-bred animals occurs as a result of persistent viral infection, mimicking human hepatitis B virus-induced HCC development. We highlight how this model addresses key gaps associated with other commonly used tumor models. We employed this model to (1) track organ biodistribution of gold NPs after intravenous administration, (2) examine their subcellular localization in the liver, (3) determine clearance kinetics, and (4) characterize the identity of hepatic macrophages that take up NPs using RNA-sequencing (RNA-seq). We found that the liver and spleen were the primary sites of NP accumulation. Subcellular analyses revealed accumulation of NPs in the lysosomes of CD14+ cells. Through RNA-seq, we uncovered that immunosuppressive macrophages within the woodchuck liver are the major cell type that take up injected NPs. The woodchuck-HCC model has the potential to be an invaluable tool to examine NP-based immune modifiers that promote host anti-tumor immunity.\n
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\n \n\n \n \n \n \n \n \n Nano Research for COVID-19.\n \n \n \n \n\n\n \n Chan, W. C. W.\n\n\n \n\n\n\n ACS Nano, 14(4): 3719–3720. April 2020.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"NanoPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{chan_nano_2020,\n\ttitle = {Nano {Research} for {COVID}-19},\n\tvolume = {14},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.0c02540},\n\tdoi = {10.1021/acsnano.0c02540},\n\tnumber = {4},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Chan, Warren C. W.},\n\tmonth = apr,\n\tyear = {2020},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {3719--3720},\n\tfile = {Full Text PDF:files/1813/Chan - 2020 - Nano Research for COVID-19.pdf:application/pdf;ACS Full Text Snapshot:files/1817/acsnano.html:text/html},\n}\n\n
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\n \n\n \n \n \n \n \n \n Diagnosing COVID-19: The Disease and Tools for Detection.\n \n \n \n \n\n\n \n Udugama, B., Kadhiresan, P., Kozlowski, H. N., Malekjahani, A., Osborne, M., Li, V. Y. C., Chen, H., Mubareka, S., Gubbay, J. B., & Chan, W. C. W.\n\n\n \n\n\n\n ACS Nano, 14(4): 3822–3835. April 2020.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"DiagnosingPaper\n  \n \n \n \"Diagnosing paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{udugama_diagnosing_2020,\n\ttitle = {Diagnosing {COVID}-19: {The} {Disease} and {Tools} for {Detection}},\n\tvolume = {14},\n\tissn = {1936-0851},\n\tshorttitle = {Diagnosing {COVID}-19},\n\turl = {https://doi.org/10.1021/acsnano.0c02624},\n\tdoi = {10.1021/acsnano.0c02624},\n\tabstract = {COVID-19 has spread globally since its discovery in Hubei province, China in December 2019. A combination of computed tomography imaging, whole genome sequencing, and electron microscopy were initially used to screen and identify SARS-CoV-2, the viral etiology of COVID-19. The aim of this review article is to inform the audience of diagnostic and surveillance technologies for SARS-CoV-2 and their performance characteristics. We describe point-of-care diagnostics that are on the horizon and encourage academics to advance their technologies beyond conception. Developing plug-and-play diagnostics to manage the SARS-CoV-2 outbreak would be useful in preventing future epidemics.},\n\tnumber = {4},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Udugama, Buddhisha and Kadhiresan, Pranav and Kozlowski, Hannah N. and Malekjahani, Ayden and Osborne, Matthew and Li, Vanessa Y. C. and Chen, Hongmin and Mubareka, Samira and Gubbay, Jonathan B. and Chan, Warren C. W.},\n\tmonth = apr,\n\tyear = {2020},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {3822--3835},\n\tfile = {Full Text PDF:files/1815/Udugama et al. - 2020 - Diagnosing COVID-19 The Disease and Tools for Det.pdf:application/pdf;ACS Full Text Snapshot:files/1822/acsnano.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acsnano.0c02624-min.pdf}\n}\n\n
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\n COVID-19 has spread globally since its discovery in Hubei province, China in December 2019. A combination of computed tomography imaging, whole genome sequencing, and electron microscopy were initially used to screen and identify SARS-CoV-2, the viral etiology of COVID-19. The aim of this review article is to inform the audience of diagnostic and surveillance technologies for SARS-CoV-2 and their performance characteristics. We describe point-of-care diagnostics that are on the horizon and encourage academics to advance their technologies beyond conception. Developing plug-and-play diagnostics to manage the SARS-CoV-2 outbreak would be useful in preventing future epidemics.\n
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\n \n\n \n \n \n \n \n \n Tunable and precise miniature lithium heater for point-of-care applications.\n \n \n \n \n\n\n \n Udugama, B., Kadhiresan, P., & Chan, W. C. W.\n\n\n \n\n\n\n PNAS, 117(9): 4632–4641. March 2020.\n Publisher: National Academy of Sciences Section: Biological Sciences\n\n\n\n
\n\n\n\n \n \n \"TunablePaper\n  \n \n \n \"Tunable paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n\n\n\n
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@article{udugama_tunable_2020,\n\ttitle = {Tunable and precise miniature lithium heater for point-of-care applications},\n\tvolume = {117},\n\tcopyright = {© 2020 . https://www.pnas.org/site/aboutpnas/licenses.xhtmlPublished under the PNAS license.},\n\tissn = {0027-8424, 1091-6490},\n\turl = {https://www.pnas.org/content/117/9/4632},\n\tdoi = {10.1073/pnas.1916562117},\n\tabstract = {Point-of-care diagnostic assays often involve multistep reactions, requiring a wide range of precise temperatures. Although precise heating is critical to performing these assays, it is challenging to provide it in an electricity-free format away from established infrastructure. Chemical heaters are electricity-free and use exothermic reactions. However, they are unsuitable for point-of-care multistep reactions because they sacrifice portability, have a narrow range of achievable temperatures, and long ramp-up times. Here we developed a miniature heater by modulating the lithium–water reaction kinetics using bubbles in a channel. Our heaters are up to 8,000 times smaller than current devices and can provide precise (within 5 °C) and tunable heating from 37 °C to 65 °C (∆TRT = 12 °C to 40 °C) with ramp-up times of a minute. We demonstrate field portablity and stability and show their use in an electricity-free multistep workflow that needs a range of temperatures. Ultimately, we envision providing better access to cutting edge biochemical techniques, including diagnostics, by making portable and electricity-free heating available at any location.},\n\tlanguage = {en},\n\tnumber = {9},\n\turldate = {2021-11-06},\n\tjournal = {PNAS},\n\tauthor = {Udugama, Buddhisha and Kadhiresan, Pranav and Chan, Warren C. W.},\n\tmonth = mar,\n\tyear = {2020},\n\tpmid = {32071225},\n\tnote = {Publisher: National Academy of Sciences\nSection: Biological Sciences},\n\tkeywords = {chemical heater, diagnostics, point of care},\n\tpages = {4632--4641},\n\tfile = {Full Text PDF:files/1820/Udugama et al. - 2020 - Tunable and precise miniature lithium heater for p.pdf:application/pdf;Snapshot:files/1821/4632.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/4632.full_.pdf}\n}\n\n
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\n Point-of-care diagnostic assays often involve multistep reactions, requiring a wide range of precise temperatures. Although precise heating is critical to performing these assays, it is challenging to provide it in an electricity-free format away from established infrastructure. Chemical heaters are electricity-free and use exothermic reactions. However, they are unsuitable for point-of-care multistep reactions because they sacrifice portability, have a narrow range of achievable temperatures, and long ramp-up times. Here we developed a miniature heater by modulating the lithium–water reaction kinetics using bubbles in a channel. Our heaters are up to 8,000 times smaller than current devices and can provide precise (within 5 °C) and tunable heating from 37 °C to 65 °C (∆TRT = 12 °C to 40 °C) with ramp-up times of a minute. We demonstrate field portablity and stability and show their use in an electricity-free multistep workflow that needs a range of temperatures. Ultimately, we envision providing better access to cutting edge biochemical techniques, including diagnostics, by making portable and electricity-free heating available at any location.\n
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\n \n\n \n \n \n \n \n \n Endothelialized collagen based pseudo-islets enables tuneable subcutaneous diabetes therapy.\n \n \n \n \n\n\n \n Vlahos, A. E., Kinney, S. M., Kingston, B. R., Keshavjee, S., Won, S., Martyts, A., Chan, W. C. W., & Sefton, M. V.\n\n\n \n\n\n\n Biomaterials, 232: 119710. February 2020.\n \n\n\n\n
\n\n\n\n \n \n \"EndothelializedPaper\n  \n \n \n \"Endothelialized paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{vlahos_endothelialized_2020,\n\ttitle = {Endothelialized collagen based pseudo-islets enables tuneable subcutaneous diabetes therapy},\n\tvolume = {232},\n\tissn = {0142-9612},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0142961219308282},\n\tdoi = {10.1016/j.biomaterials.2019.119710},\n\tabstract = {Pancreatic islets are fragile cell clusters and many isolated islets are not suitable for transplantation. Furthermore, following transplantation, islets will experience a state of hypoxia and poor nutrient diffusion before revascularization, which is detrimental to islet survival; this is affected by islet size and health. Here we engineered tuneable size-controlled pseudo-islets created by dispersing de-aggregated islets in an endothelialized collagen scaffold. This supported subcutaneous engraftment, which returned streptozotocin-induced diabetic mice to normoglycemia. Whole-implant imaging after tissue clearing demonstrated pseudo-islets regenerated their vascular architecture and insulin-secreting β-cells were within 5 μm of a perfusable vessel – a feature unique to this approach. By using an endothelialized collagen scaffold, this work highlights a novel “bottom-up” approach to islet engineering that provides control over the size and composition of the constructs, while enabling the critical ability to revascularize and engraft when transplanted into the clinically useful subcutaneous space.},\n\tlanguage = {en},\n\turldate = {2021-11-06},\n\tjournal = {Biomaterials},\n\tauthor = {Vlahos, Alexander E. and Kinney, Sean M. and Kingston, Benjamin R. and Keshavjee, Sara and Won, So-Yoon and Martyts, Anastasiya and Chan, Warren C. W. and Sefton, Michael V.},\n\tmonth = feb,\n\tyear = {2020},\n\tkeywords = {CLARITY, Diabetes, Endothelialized collagen scaffold, Modular tissue engineering, Pseudo-islets, Subcutaneous islet transplantation, Vascularization},\n\tpages = {119710},\n\tfile = {ScienceDirect Full Text PDF:files/1826/Vlahos et al. - 2020 - Endothelialized collagen based pseudo-islets enabl.pdf:application/pdf},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/1-s2.0-S0142961219308282-main-min.pdf}\n}\n\n
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\n Pancreatic islets are fragile cell clusters and many isolated islets are not suitable for transplantation. Furthermore, following transplantation, islets will experience a state of hypoxia and poor nutrient diffusion before revascularization, which is detrimental to islet survival; this is affected by islet size and health. Here we engineered tuneable size-controlled pseudo-islets created by dispersing de-aggregated islets in an endothelialized collagen scaffold. This supported subcutaneous engraftment, which returned streptozotocin-induced diabetic mice to normoglycemia. Whole-implant imaging after tissue clearing demonstrated pseudo-islets regenerated their vascular architecture and insulin-secreting β-cells were within 5 μm of a perfusable vessel – a feature unique to this approach. By using an endothelialized collagen scaffold, this work highlights a novel “bottom-up” approach to islet engineering that provides control over the size and composition of the constructs, while enabling the critical ability to revascularize and engraft when transplanted into the clinically useful subcutaneous space.\n
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\n \n\n \n \n \n \n \n \n Liposome Imaging in Optically Cleared Tissues.\n \n \n \n \n\n\n \n Syed, A. M., MacMillan, P., Ngai, J., Wilhelm, S., Sindhwani, S., Kingston, B. R., Wu, J. L. Y., Llano-Suárez, P., Lin, Z. P., Ouyang, B., Kahiel, Z., Gadde, S., & Chan, W. C. W.\n\n\n \n\n\n\n Nano Lett., 20(2): 1362–1369. February 2020.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"LiposomePaper\n  \n \n \n \"Liposome paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{syed_liposome_2020,\n\ttitle = {Liposome {Imaging} in {Optically} {Cleared} {Tissues}},\n\tvolume = {20},\n\tissn = {1530-6984},\n\turl = {https://doi.org/10.1021/acs.nanolett.9b04853},\n\tdoi = {10.1021/acs.nanolett.9b04853},\n\tabstract = {Three-dimensional (3D) optical microscopy can be used to understand and improve the delivery of nanomedicine. However, this approach cannot be performed for analyzing liposomes in tissues because the processing step to make tissues transparent for imaging typically removes the lipids. Here, we developed a tag, termed REMNANT, that enables 3D imaging of organic materials in biological tissues. We demonstrated the utility of this tag for the 3D mapping of liposomes in intact tissues. We also showed that the tag is able to monitor the release of entrapped therapeutic agents. We found that liposomes release their cargo {\\textgreater}100-fold faster in tissues in vivo than in conventional in vitro assays. This allowed us to design a liposomal formulation with enhanced ability to kill tumor associated macrophages. Our development opens up new opportunities for studying the chemical properties and pharmacodynamics of administered organic materials in an intact biological environment. This approach provides insight into the in vivo behavior of degradable materials, where the newly discovered information can guide the engineering of the next generation of imaging and therapeutic agents.},\n\tnumber = {2},\n\turldate = {2021-11-06},\n\tjournal = {Nano Lett.},\n\tauthor = {Syed, Abdullah Muhammad and MacMillan, Presley and Ngai, Jessica and Wilhelm, Stefan and Sindhwani, Shrey and Kingston, Benjamin R. and Wu, Jamie L. Y. and Llano-Suárez, Pablo and Lin, Zachary Pengju and Ouyang, Ben and Kahiel, Zaina and Gadde, Suresh and Chan, Warren C. W.},\n\tmonth = feb,\n\tyear = {2020},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {1362--1369},\n\tfile = {Full Text PDF:files/1830/Syed et al. - 2020 - Liposome Imaging in Optically Cleared Tissues.pdf:application/pdf;ACS Full Text Snapshot:files/1832/acs.nanolett.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acs.nanolett.9b04853-min.pdf}\n}\n\n
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\n Three-dimensional (3D) optical microscopy can be used to understand and improve the delivery of nanomedicine. However, this approach cannot be performed for analyzing liposomes in tissues because the processing step to make tissues transparent for imaging typically removes the lipids. Here, we developed a tag, termed REMNANT, that enables 3D imaging of organic materials in biological tissues. We demonstrated the utility of this tag for the 3D mapping of liposomes in intact tissues. We also showed that the tag is able to monitor the release of entrapped therapeutic agents. We found that liposomes release their cargo \\textgreater100-fold faster in tissues in vivo than in conventional in vitro assays. This allowed us to design a liposomal formulation with enhanced ability to kill tumor associated macrophages. Our development opens up new opportunities for studying the chemical properties and pharmacodynamics of administered organic materials in an intact biological environment. This approach provides insight into the in vivo behavior of degradable materials, where the newly discovered information can guide the engineering of the next generation of imaging and therapeutic agents.\n
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\n  \n 2019\n \n \n (9)\n \n \n
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\n \n\n \n \n \n \n \n \n The Future of Nanotechnology: Cross-disciplined Progress to Improve Health and Medicine.\n \n \n \n \n\n\n \n Cheon, J., Chan, W., & Zuhorn, I.\n\n\n \n\n\n\n Acc. Chem. Res., 52(9): 2405–2405. September 2019.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"ThePaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n  \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{cheon_future_2019,\n\ttitle = {The {Future} of {Nanotechnology}: {Cross}-disciplined {Progress} to {Improve} {Health} and {Medicine}},\n\tvolume = {52},\n\tissn = {0001-4842},\n\tshorttitle = {The {Future} of {Nanotechnology}},\n\turl = {https://doi.org/10.1021/acs.accounts.9b00423},\n\tdoi = {10.1021/acs.accounts.9b00423},\n\tnumber = {9},\n\turldate = {2021-11-06},\n\tjournal = {Acc. Chem. Res.},\n\tauthor = {Cheon, Jinwoo and Chan, Warren and Zuhorn, Inge},\n\tmonth = sep,\n\tyear = {2019},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {2405--2405},\n\tfile = {Full Text PDF:files/1829/Cheon et al. - 2019 - The Future of Nanotechnology Cross-disciplined Pr.pdf:application/pdf;ACS Full Text Snapshot:files/1831/acs.accounts.html:text/html},\n}\n\n
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\n \n\n \n \n \n \n \n \n Engineering Steps for Mobile Point-of-Care Diagnostic Devices.\n \n \n \n \n\n\n \n Malekjahani, A., Sindhwani, S., Syed, A. M., & Chan, W. C. W.\n\n\n \n\n\n\n Acc. Chem. Res., 52(9): 2406–2414. September 2019.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"EngineeringPaper\n  \n \n \n \"Engineering paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{malekjahani_engineering_2019,\n\ttitle = {Engineering {Steps} for {Mobile} {Point}-of-{Care} {Diagnostic} {Devices}},\n\tvolume = {52},\n\tissn = {0001-4842},\n\turl = {https://doi.org/10.1021/acs.accounts.9b00200},\n\tdoi = {10.1021/acs.accounts.9b00200},\n\tabstract = {ConspectusMobile phone technology is a perfect companion for point-of-care diagnostics as they come equipped with advanced processors, high resolution cameras, and network connectivity. Despite several academic pursuits, only a few mobile phone diagnostics have been tested in the field, commercialized or achieved regulatory approval. This review will address the challenges associated with developing mobile diagnostics and suggest strategies to overcome them. We aim to provide a resource for researchers to accelerate the development of new diagnostics. Our Account includes an overview of published mobile phone diagnostics and highlights lessons learned from their approach to diagnostic development. Also, we have included recommendations from regulatory and public health agencies, such as the U.S. Food and Drug Administration and World Health Organization, to further guide researchers.We believe that the development of mobile phone point-of-care diagnostics takes place in four distinct steps: (1) Needs and Value Assessment, (2) Technology Development, (3) Preclinical Verification, and (4) Clinical Validation and Field Trials. During each step, we outline developmental strategies to help researchers avoid potential challenges. (1) Researchers commonly develop devices to maximize technical parameters such as sensitivity and time which do not necessarily translate to increased clinical impact. Researchers must focus on assessing specific diagnostic needs and the value which a potential device would offer. (2) Often, researchers claim they have developed devices for feasible implementation at the point-of-care, yet they rely on laboratory resources. Researchers must develop equipment-free devices which are agnostic to any mobile phone. (3) Another challenge researchers face is decreased performance during field evaluations relative to initial laboratory verification. Researchers must ensure that they simulate the field conditions during laboratory verification to achieve successful translation. (4) Finally, proper field testing of devices must be performed in conditions which match that of the final intended use.The future of mobile phone point-of-care diagnostic devices is bright and has the potential to radically change how patients are diagnosed. Before we reach this point, researchers must take a step backward and focus on the first-principles of basic research. The widespread adoption and rapid scaling of these devices can only be achieved once the fundamentals have been considered. The insights and strategies provided here will help researchers avoid pitfalls, streamline development and make better decisions during the development of new diagnostics. Further, we believe this Account can help push the field of mobile diagnostics toward increased productivity, leading to more approved devices and ultimately helping curb the burden of disease worldwide.},\n\tnumber = {9},\n\turldate = {2021-11-06},\n\tjournal = {Acc. Chem. Res.},\n\tauthor = {Malekjahani, Ayden and Sindhwani, Shrey and Syed, Abdullah Muhammad and Chan, Warren C. W.},\n\tmonth = sep,\n\tyear = {2019},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {2406--2414},\n\tfile = {Full Text PDF:files/1835/Malekjahani et al. - 2019 - Engineering Steps for Mobile Point-of-Care Diagnos.pdf:application/pdf;ACS Full Text Snapshot:files/1840/acs.accounts.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acs.accounts.9b00200-min.pdf}\n}\n\n
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\n ConspectusMobile phone technology is a perfect companion for point-of-care diagnostics as they come equipped with advanced processors, high resolution cameras, and network connectivity. Despite several academic pursuits, only a few mobile phone diagnostics have been tested in the field, commercialized or achieved regulatory approval. This review will address the challenges associated with developing mobile diagnostics and suggest strategies to overcome them. We aim to provide a resource for researchers to accelerate the development of new diagnostics. Our Account includes an overview of published mobile phone diagnostics and highlights lessons learned from their approach to diagnostic development. Also, we have included recommendations from regulatory and public health agencies, such as the U.S. Food and Drug Administration and World Health Organization, to further guide researchers.We believe that the development of mobile phone point-of-care diagnostics takes place in four distinct steps: (1) Needs and Value Assessment, (2) Technology Development, (3) Preclinical Verification, and (4) Clinical Validation and Field Trials. During each step, we outline developmental strategies to help researchers avoid potential challenges. (1) Researchers commonly develop devices to maximize technical parameters such as sensitivity and time which do not necessarily translate to increased clinical impact. Researchers must focus on assessing specific diagnostic needs and the value which a potential device would offer. (2) Often, researchers claim they have developed devices for feasible implementation at the point-of-care, yet they rely on laboratory resources. Researchers must develop equipment-free devices which are agnostic to any mobile phone. (3) Another challenge researchers face is decreased performance during field evaluations relative to initial laboratory verification. Researchers must ensure that they simulate the field conditions during laboratory verification to achieve successful translation. (4) Finally, proper field testing of devices must be performed in conditions which match that of the final intended use.The future of mobile phone point-of-care diagnostic devices is bright and has the potential to radically change how patients are diagnosed. Before we reach this point, researchers must take a step backward and focus on the first-principles of basic research. The widespread adoption and rapid scaling of these devices can only be achieved once the fundamentals have been considered. The insights and strategies provided here will help researchers avoid pitfalls, streamline development and make better decisions during the development of new diagnostics. Further, we believe this Account can help push the field of mobile diagnostics toward increased productivity, leading to more approved devices and ultimately helping curb the burden of disease worldwide.\n
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\n \n\n \n \n \n \n \n \n Nanoparticle Size Influences Antigen Retention and Presentation in Lymph Node Follicles for Humoral Immunity.\n \n \n \n \n\n\n \n Zhang, Y., Lazarovits, J., Poon, W., Ouyang, B., Nguyen, L. N. M., Kingston, B. R., & Chan, W. C. W.\n\n\n \n\n\n\n Nano Lett., 19(10): 7226–7235. October 2019.\n Publisher: American Chemical Society\n\n\n\n
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@article{zhang_nanoparticle_2019,\n\ttitle = {Nanoparticle {Size} {Influences} {Antigen} {Retention} and {Presentation} in {Lymph} {Node} {Follicles} for {Humoral} {Immunity}},\n\tvolume = {19},\n\tissn = {1530-6984},\n\turl = {https://doi.org/10.1021/acs.nanolett.9b02834},\n\tdoi = {10.1021/acs.nanolett.9b02834},\n\tabstract = {Lymph node follicles capture and retain antigens to induce germinal centers and long-lived humoral immunity. However, control over antigen retention has been limited. Here we discovered that antigen conjugated to nanoparticle carriers of different sizes impacts the intralymph node transport and specific cell interaction. We found that follicular dendritic cell (FDC) networks determine the intralymph node follicle fate of these nanoparticles by clearing smaller ones (5–15 nm) within 48 h and retaining larger ones (50–100 nm) for over 5 weeks. The 50–100 nm-sized nanoparticles had 175-fold more delivery of antigen at the FDC dendrites, 5-fold enhanced humoral immune responses of germinal center B cell formation, and 5-fold more antigen-specific antibody production over 5–15 nm nanoparticles. Our results show that we can tune humoral immunity by simply manipulating the carrier size design to produce effectiveness of vaccines.},\n\tnumber = {10},\n\turldate = {2021-11-06},\n\tjournal = {Nano Lett.},\n\tauthor = {Zhang, Yi-Nan and Lazarovits, James and Poon, Wilson and Ouyang, Ben and Nguyen, Luan N. M. and Kingston, Benjamin R. and Chan, Warren C. W.},\n\tmonth = oct,\n\tyear = {2019},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {7226--7235},\n\tfile = {Full Text PDF:files/1841/Zhang et al. - 2019 - Nanoparticle Size Influences Antigen Retention and.pdf:application/pdf;ACS Full Text Snapshot:files/1842/acs.nanolett.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acs.nanolett.9b02834-min.pdf}\n}\n\n
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\n Lymph node follicles capture and retain antigens to induce germinal centers and long-lived humoral immunity. However, control over antigen retention has been limited. Here we discovered that antigen conjugated to nanoparticle carriers of different sizes impacts the intralymph node transport and specific cell interaction. We found that follicular dendritic cell (FDC) networks determine the intralymph node follicle fate of these nanoparticles by clearing smaller ones (5–15 nm) within 48 h and retaining larger ones (50–100 nm) for over 5 weeks. The 50–100 nm-sized nanoparticles had 175-fold more delivery of antigen at the FDC dendrites, 5-fold enhanced humoral immune responses of germinal center B cell formation, and 5-fold more antigen-specific antibody production over 5–15 nm nanoparticles. Our results show that we can tune humoral immunity by simply manipulating the carrier size design to produce effectiveness of vaccines.\n
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\n \n\n \n \n \n \n \n \n Assessing micrometastases as a target for nanoparticles using 3D microscopy and machine learning.\n \n \n \n \n\n\n \n Kingston, B. R., Syed, A. M., Ngai, J., Sindhwani, S., & Chan, W. C. W.\n\n\n \n\n\n\n PNAS, 116(30): 14937–14946. July 2019.\n ISBN: 9781907646119 Publisher: National Academy of Sciences Section: PNAS Plus\n\n\n\n
\n\n\n\n \n \n \"AssessingPaper\n  \n \n \n \"Assessing paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{kingston_assessing_2019,\n\ttitle = {Assessing micrometastases as a target for nanoparticles using {3D} microscopy and machine learning},\n\tvolume = {116},\n\tcopyright = {© 2019 . https://www-pnas-org.myaccess.library.utoronto.ca/site/aboutpnas/licenses.xhtmlPublished under the PNAS license.},\n\tissn = {0027-8424, 1091-6490},\n\turl = {http://www.pnas.org/content/116/30/14937},\n\tdoi = {10.1073/pnas.1907646116},\n\tabstract = {Metastasis of solid tumors is a key determinant of cancer patient survival. Targeting micrometastases using nanoparticles could offer a way to stop metastatic tumor growth before it causes excessive patient morbidity. However, nanoparticle delivery to micrometastases is difficult to investigate because micrometastases are small in size and lie deep within tissues. Here, we developed an imaging and image analysis workflow to analyze nanoparticle–cell interactions in metastatic tumors. This technique combines tissue clearing and 3D microscopy with machine learning-based image analysis to assess the physiology of micrometastases with single-cell resolution and quantify the delivery of nanoparticles within them. We show that nanoparticles access a higher proportion of cells in micrometastases (50\\% nanoparticle-positive cells) compared with primary tumors (17\\% nanoparticle-positive cells) because they reside close to blood vessels and require a small diffusion distance to reach all tumor cells. Furthermore, the high-throughput nature of our image analysis workflow allowed us to profile the physiology and nanoparticle delivery of 1,301 micrometastases. This enabled us to use machine learning-based modeling to predict nanoparticle delivery to individual micrometastases based on their physiology. Our imaging method allows researchers to measure nanoparticle delivery to micrometastases and highlights an opportunity to target micrometastases with nanoparticles. The development of models to predict nanoparticle delivery based on micrometastasis physiology could enable personalized treatments based on the specific physiology of a patient’s micrometastases.},\n\tlanguage = {en},\n\tnumber = {30},\n\turldate = {2021-11-06},\n\tjournal = {PNAS},\n\tauthor = {Kingston, Benjamin R. and Syed, Abdullah Muhammad and Ngai, Jessica and Sindhwani, Shrey and Chan, Warren C. W.},\n\tmonth = jul,\n\tyear = {2019},\n\tpmid = {31285340},\n\tnote = {ISBN: 9781907646119\nPublisher: National Academy of Sciences\nSection: PNAS Plus},\n\tkeywords = {3D microscopy, image analysis, machine learning, metastasis, nanoparticles},\n\tpages = {14937--14946},\n\tfile = {Full Text PDF:files/1844/Kingston et al. - 2019 - Assessing micrometastases as a target for nanopart.pdf:application/pdf;Snapshot:files/1846/14937.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2022/01/KINGST1-1.pdf}\n}\n\n
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\n Metastasis of solid tumors is a key determinant of cancer patient survival. Targeting micrometastases using nanoparticles could offer a way to stop metastatic tumor growth before it causes excessive patient morbidity. However, nanoparticle delivery to micrometastases is difficult to investigate because micrometastases are small in size and lie deep within tissues. Here, we developed an imaging and image analysis workflow to analyze nanoparticle–cell interactions in metastatic tumors. This technique combines tissue clearing and 3D microscopy with machine learning-based image analysis to assess the physiology of micrometastases with single-cell resolution and quantify the delivery of nanoparticles within them. We show that nanoparticles access a higher proportion of cells in micrometastases (50% nanoparticle-positive cells) compared with primary tumors (17% nanoparticle-positive cells) because they reside close to blood vessels and require a small diffusion distance to reach all tumor cells. Furthermore, the high-throughput nature of our image analysis workflow allowed us to profile the physiology and nanoparticle delivery of 1,301 micrometastases. This enabled us to use machine learning-based modeling to predict nanoparticle delivery to individual micrometastases based on their physiology. Our imaging method allows researchers to measure nanoparticle delivery to micrometastases and highlights an opportunity to target micrometastases with nanoparticles. The development of models to predict nanoparticle delivery based on micrometastasis physiology could enable personalized treatments based on the specific physiology of a patient’s micrometastases.\n
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\n \n\n \n \n \n \n \n \n Characterizing the protein corona of sub-10 nm nanoparticles.\n \n \n \n \n\n\n \n Glancy, D., Zhang, Y., Wu, J. L. Y., Ouyang, B., Ohta, S., & Chan, W. C. W.\n\n\n \n\n\n\n Journal of Controlled Release, 304: 102–110. June 2019.\n \n\n\n\n
\n\n\n\n \n \n \"CharacterizingPaper\n  \n \n \n \"Characterizing paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{glancy_characterizing_2019,\n\ttitle = {Characterizing the protein corona of sub-10 nm nanoparticles},\n\tvolume = {304},\n\tissn = {0168-3659},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0168365919302238},\n\tdoi = {10.1016/j.jconrel.2019.04.023},\n\tabstract = {Studies into the interactions of serum proteins with nanoparticles are typically performed using nanoparticles that are larger than the size of proteins. Due to this size discrepancy, adsorbed proteins are commonly depicted as a globular structure surrounding a nanoparticle. Here, we asked how we should view nanoparticle–protein complexes when the nanoparticles are of similar size or smaller than the proteins with which they interact. We showed that nanoparticles can serve as a cargo on a protein rather than as a carrier of the protein in a size-dependent manner. This can occur when nanoparticles are below 10 nm in diameter. We discovered that when the nanoparticle is a cargo on the protein, the binding of the protein to the receptor target is minimally affected in contrast to the nanoparticle serving as a carrier. Our study should change how we view and describe nanoparticle–protein complexes when the nanoparticles involved are equal in size or smaller than proteins.},\n\tlanguage = {en},\n\turldate = {2021-11-06},\n\tjournal = {Journal of Controlled Release},\n\tauthor = {Glancy, Dylan and Zhang, Yuwei and Wu, Jamie L. Y. and Ouyang, Ben and Ohta, Seiichi and Chan, Warren C. W.},\n\tmonth = jun,\n\tyear = {2019},\n\tkeywords = {Cargo, Carrier, Nanomedicine, Protein corona, Ultrasmall nanoparticles},\n\tpages = {102--110},\n\tfile = {ScienceDirect Full Text PDF:files/1848/Glancy et al. - 2019 - Characterizing the protein corona of sub-10 nm nan.pdf:application/pdf},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/1-s2.0-S0168365919302238-main.pdf}\n}\n\n
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\n Studies into the interactions of serum proteins with nanoparticles are typically performed using nanoparticles that are larger than the size of proteins. Due to this size discrepancy, adsorbed proteins are commonly depicted as a globular structure surrounding a nanoparticle. Here, we asked how we should view nanoparticle–protein complexes when the nanoparticles are of similar size or smaller than the proteins with which they interact. We showed that nanoparticles can serve as a cargo on a protein rather than as a carrier of the protein in a size-dependent manner. This can occur when nanoparticles are below 10 nm in diameter. We discovered that when the nanoparticle is a cargo on the protein, the binding of the protein to the receptor target is minimally affected in contrast to the nanoparticle serving as a carrier. Our study should change how we view and describe nanoparticle–protein complexes when the nanoparticles involved are equal in size or smaller than proteins.\n
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\n \n\n \n \n \n \n \n \n Supervised Learning and Mass Spectrometry Predicts the in Vivo Fate of Nanomaterials.\n \n \n \n \n\n\n \n Lazarovits, J., Sindhwani, S., Tavares, A. J., Zhang, Y., Song, F., Audet, J., Krieger, J. R., Syed, A. M., Stordy, B., & Chan, W. C. W.\n\n\n \n\n\n\n ACS Nano, 13(7): 8023–8034. July 2019.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"SupervisedPaper\n  \n \n \n \"Supervised paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{lazarovits_supervised_2019,\n\ttitle = {Supervised {Learning} and {Mass} {Spectrometry} {Predicts} the in {Vivo} {Fate} of {Nanomaterials}},\n\tvolume = {13},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.9b02774},\n\tdoi = {10.1021/acsnano.9b02774},\n\tabstract = {The surface of nanoparticles changes immediately after intravenous injection because blood proteins adsorb on the surface. How this interface changes during circulation and its impact on nanoparticle distribution within the body is not understood. Here, we developed a workflow to show that the evolution of proteins on nanoparticle surfaces predicts the biological fate of nanoparticles in vivo. This workflow involves extracting nanoparticles at multiple time points from circulation, isolating the proteins off the surface and performing proteomic mass spectrometry. The mass spectrometry protein library served as inputs, while blood clearance and organ accumulation were used as outputs to train a supervised deep neural network that predicts nanoparticle biological fate. In a double-blinded study, we tested the network by predicting nanoparticle spleen and liver accumulation with upward of 94\\% accuracy. Our neural network discovered that the mechanism of liver and spleen uptake is due to patterns of a multitude of nanoparticle surface adsorbed proteins. There are too many combinations to change these proteins manually using chemical or biological inhibitors to alter clearance. Therefore, we developed a technique that uses the host to act as a bioreactor to prepare nanoparticles with predictable clearance patterns that reduce liver and spleen uptake by 50\\% and 70\\%, respectively. These techniques provide opportunities to both predict nanoparticle behavior and also to engineer surface chemistries that are specifically designed by the body.},\n\tnumber = {7},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Lazarovits, James and Sindhwani, Shrey and Tavares, Anthony J. and Zhang, Yuwei and Song, Fayi and Audet, Julie and Krieger, Jonathan R. and Syed, Abdullah Muhammad and Stordy, Benjamin and Chan, Warren C. W.},\n\tmonth = jul,\n\tyear = {2019},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {8023--8034},\n\tfile = {Full Text PDF:files/1850/Lazarovits et al. - 2019 - Supervised Learning and Mass Spectrometry Predicts.pdf:application/pdf;ACS Full Text Snapshot:files/1859/acsnano.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acsnano.9b02774-min.pdf}\n}\n\n
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\n The surface of nanoparticles changes immediately after intravenous injection because blood proteins adsorb on the surface. How this interface changes during circulation and its impact on nanoparticle distribution within the body is not understood. Here, we developed a workflow to show that the evolution of proteins on nanoparticle surfaces predicts the biological fate of nanoparticles in vivo. This workflow involves extracting nanoparticles at multiple time points from circulation, isolating the proteins off the surface and performing proteomic mass spectrometry. The mass spectrometry protein library served as inputs, while blood clearance and organ accumulation were used as outputs to train a supervised deep neural network that predicts nanoparticle biological fate. In a double-blinded study, we tested the network by predicting nanoparticle spleen and liver accumulation with upward of 94% accuracy. Our neural network discovered that the mechanism of liver and spleen uptake is due to patterns of a multitude of nanoparticle surface adsorbed proteins. There are too many combinations to change these proteins manually using chemical or biological inhibitors to alter clearance. Therefore, we developed a technique that uses the host to act as a bioreactor to prepare nanoparticles with predictable clearance patterns that reduce liver and spleen uptake by 50% and 70%, respectively. These techniques provide opportunities to both predict nanoparticle behavior and also to engineer surface chemistries that are specifically designed by the body.\n
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\n \n\n \n \n \n \n \n \n Redefining the Experimental and Methods Sections.\n \n \n \n \n\n\n \n Millstone, J. E., Chan, W. C. W., Kagan, C. R., Liz-Marzán, L. M., Kotov, N. A., Mulvaney, P. A., Parak, W. J., Rogach, A. L., Weiss, P. S., & Schaak, R. E.\n\n\n \n\n\n\n ACS Nano, 13(5): 4862–4864. May 2019.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"RedefiningPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{millstone_redefining_2019,\n\ttitle = {Redefining the {Experimental} and {Methods} {Sections}},\n\tvolume = {13},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.9b03753},\n\tdoi = {10.1021/acsnano.9b03753},\n\tnumber = {5},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Millstone, Jill E. and Chan, Warren C. W. and Kagan, Cherie R. and Liz-Marzán, Luis M. and Kotov, Nicholas A. and Mulvaney, Paul A. and Parak, Wolfgang J. and Rogach, Andrey L. and Weiss, Paul S. and Schaak, Raymond E.},\n\tmonth = may,\n\tyear = {2019},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {4862--4864},\n\tfile = {Full Text PDF:files/1852/Millstone et al. - 2019 - Redefining the Experimental and Methods Sections.pdf:application/pdf;ACS Full Text Snapshot:files/1855/acsnano.html:text/html},\n}\n\n
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\n \n\n \n \n \n \n \n \n Elimination Pathways of Nanoparticles.\n \n \n \n \n\n\n \n Poon, W., Zhang, Y., Ouyang, B., Kingston, B. R., Wu, J. L. Y., Wilhelm, S., & Chan, W. C. W.\n\n\n \n\n\n\n ACS Nano, 13(5): 5785–5798. May 2019.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"EliminationPaper\n  \n \n \n \"Elimination paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{poon_elimination_2019,\n\ttitle = {Elimination {Pathways} of {Nanoparticles}},\n\tvolume = {13},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.9b01383},\n\tdoi = {10.1021/acsnano.9b01383},\n\tabstract = {Understanding how nanoparticles are eliminated from the body is required for their successful clinical translation. Many promising nanoparticle formulations for in vivo medical applications are large ({\\textgreater}5.5 nm) and nonbiodegradable, so they cannot be eliminated renally. A proposed pathway for these nanoparticles is hepatobiliary elimination, but their transport has not been well-studied. Here, we explored the barriers that determined the elimination of nanoparticles through the hepatobiliary route. The route of hepatobiliary elimination is usually through the following pathway: (1) liver sinusoid, (2) space of Disse, (3) hepatocytes, (4) bile ducts, (5) intestines, and (6) out of the body. We discovered that the interaction of nanoparticles with liver nonparenchymal cells (e.g., Kupffer cells and liver sinusoidal endothelial cells) determines the elimination fate. Each step in the route contains cells that can sequester and chemically or physically alter the nanoparticles, which influences their fecal elimination. We showed that the removal of Kupffer cells increased fecal elimination by {\\textgreater}10 times. Combining our results with those of prior studies, we can start to build a systematic view of nanoparticle elimination pathways as it relates to particle size and other design parameters. This is critical to engineering medically useful and translatable nanotechnologies.},\n\tnumber = {5},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Poon, Wilson and Zhang, Yi-Nan and Ouyang, Ben and Kingston, Benjamin R. and Wu, Jamie L. Y. and Wilhelm, Stefan and Chan, Warren C. W.},\n\tmonth = may,\n\tyear = {2019},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {5785--5798},\n\tfile = {Full Text PDF:files/1856/Poon et al. - 2019 - Elimination Pathways of Nanoparticles.pdf:application/pdf;ACS Full Text Snapshot:files/1862/acsnano.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acsnano.9b01383-min.pdf}\n}\n\n
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\n Understanding how nanoparticles are eliminated from the body is required for their successful clinical translation. Many promising nanoparticle formulations for in vivo medical applications are large (\\textgreater5.5 nm) and nonbiodegradable, so they cannot be eliminated renally. A proposed pathway for these nanoparticles is hepatobiliary elimination, but their transport has not been well-studied. Here, we explored the barriers that determined the elimination of nanoparticles through the hepatobiliary route. The route of hepatobiliary elimination is usually through the following pathway: (1) liver sinusoid, (2) space of Disse, (3) hepatocytes, (4) bile ducts, (5) intestines, and (6) out of the body. We discovered that the interaction of nanoparticles with liver nonparenchymal cells (e.g., Kupffer cells and liver sinusoidal endothelial cells) determines the elimination fate. Each step in the route contains cells that can sequester and chemically or physically alter the nanoparticles, which influences their fecal elimination. We showed that the removal of Kupffer cells increased fecal elimination by \\textgreater10 times. Combining our results with those of prior studies, we can start to build a systematic view of nanoparticle elimination pathways as it relates to particle size and other design parameters. This is critical to engineering medically useful and translatable nanotechnologies.\n
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\n \n\n \n \n \n \n \n \n Synthesis of Patient-Specific Nanomaterials.\n \n \n \n \n\n\n \n Lazarovits, J., Chen, Y. Y., Song, F., Ngo, W., Tavares, A. J., Zhang, Y., Audet, J., Tang, B., Lin, Q., Tleugabulova, M. C., Wilhelm, S., Krieger, J. R., Mallevaey, T., & Chan, W. C. W.\n\n\n \n\n\n\n Nano Lett., 19(1): 116–123. January 2019.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"SynthesisPaper\n  \n \n \n \"Synthesis paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{lazarovits_synthesis_2019,\n\ttitle = {Synthesis of {Patient}-{Specific} {Nanomaterials}},\n\tvolume = {19},\n\tissn = {1530-6984},\n\turl = {https://doi.org/10.1021/acs.nanolett.8b03434},\n\tdoi = {10.1021/acs.nanolett.8b03434},\n\tabstract = {Nanoparticles are engineered from materials such as metals, polymers, and different carbon allotropes that do not exist within the body. Exposure to these exogenous compounds raises concerns surrounding toxicity, inflammation, and immune activation. These responses could potentially be mitigated by synthesizing nanoparticles directly from molecules derived from the host. However, efforts to assemble patient-derived macromolecules into structures with the same degree of size and shape tunability as their exogenous counterparts remains a significant challenge. Here we solve this problem by creating a new class of size- and shape-tunable personalized protein nanoparticles (PNP) made entirely from patient-derived proteins. PNPs are built into different sizes and shapes with the same degree of tunability as gold nanoparticles. They are biodegradable and do not activate innate or adaptive immunity following single and repeated administrations in vivo. PNPs can be further modified with specific protein cargos that remain catalytically active even after intracellular delivery in vivo. Finally, we demonstrate that PNPs created from different human patients have unique molecular fingerprints encoded directly into the structure of the nanoparticle. This new class of personalized nanomaterial has the potential to revolutionize how we treat patients and can become an integral component in the diagnostic and therapeutic toolbox.},\n\tnumber = {1},\n\turldate = {2021-11-06},\n\tjournal = {Nano Lett.},\n\tauthor = {Lazarovits, James and Chen, Yih Yang and Song, Fayi and Ngo, Wayne and Tavares, Anthony J. and Zhang, Yi-Nan and Audet, Julie and Tang, Bo and Lin, Qiaochu and Tleugabulova, Mayra Cruz and Wilhelm, Stefan and Krieger, Jonathan R. and Mallevaey, Thierry and Chan, Warren C. W.},\n\tmonth = jan,\n\tyear = {2019},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {116--123},\n\tfile = {Full Text PDF:files/1858/Lazarovits et al. - 2019 - Synthesis of Patient-Specific Nanomaterials.pdf:application/pdf;ACS Full Text Snapshot:files/1863/acs.nanolett.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acs.nanolett.8b03434-min.pdf}\n}\n\n
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\n Nanoparticles are engineered from materials such as metals, polymers, and different carbon allotropes that do not exist within the body. Exposure to these exogenous compounds raises concerns surrounding toxicity, inflammation, and immune activation. These responses could potentially be mitigated by synthesizing nanoparticles directly from molecules derived from the host. However, efforts to assemble patient-derived macromolecules into structures with the same degree of size and shape tunability as their exogenous counterparts remains a significant challenge. Here we solve this problem by creating a new class of size- and shape-tunable personalized protein nanoparticles (PNP) made entirely from patient-derived proteins. PNPs are built into different sizes and shapes with the same degree of tunability as gold nanoparticles. They are biodegradable and do not activate innate or adaptive immunity following single and repeated administrations in vivo. PNPs can be further modified with specific protein cargos that remain catalytically active even after intracellular delivery in vivo. Finally, we demonstrate that PNPs created from different human patients have unique molecular fingerprints encoded directly into the structure of the nanoparticle. This new class of personalized nanomaterial has the potential to revolutionize how we treat patients and can become an integral component in the diagnostic and therapeutic toolbox.\n
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\n  \n 2018\n \n \n (4)\n \n \n
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\n \n\n \n \n \n \n \n \n The 15th Anniversary of the U.S. National Nanotechnology Initiative.\n \n \n \n \n\n\n \n Chan, W. C. W., Chhowalla, M., Farokhzad, O., Glotzer, S., Gogotsi, Y., Hammond, P. T., Hersam, M. C., Javey, A., Kagan, C. R., Kataoka, K., Khademhosseini, A., Kotov, N. A., Lee, S., Lee, Y. H., Li, Y., Millstone, J. E., Mulvaney, P., Nel, A. E., Nordlander, P. J., Parak, W. J., Penner, R. M., Rogach, A. L., Schaak, R. E., Sood, A. K., Stevens, M. M., Wee, A. T. S., Weil, T., Grant Willson, C., & Weiss, P. S.\n\n\n \n\n\n\n ACS Nano, 12(11): 10567–10569. November 2018.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"ThePaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{chan_15th_2018,\n\ttitle = {The 15th {Anniversary} of the {U}.{S}. {National} {Nanotechnology} {Initiative}},\n\tvolume = {12},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.8b08676},\n\tdoi = {10.1021/acsnano.8b08676},\n\tnumber = {11},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Chan, Warren C. W. and Chhowalla, Manish and Farokhzad, Omid and Glotzer, Sharon and Gogotsi, Yury and Hammond, Paula T. and Hersam, Mark C. and Javey, Ali and Kagan, Cherie R. and Kataoka, Kazunori and Khademhosseini, Ali and Kotov, Nicholas A. and Lee, Shuit-Tong and Lee, Young Hee and Li, Yan and Millstone, Jill E. and Mulvaney, Paul and Nel, Andre E. and Nordlander, Peter J. and Parak, Wolfgang J. and Penner, Reginald M. and Rogach, Andrey L. and Schaak, Raymond E. and Sood, Ajay K. and Stevens, Molly M. and Wee, Andrew T. S. and Weil, Tanja and Grant Willson, C. and Weiss, Paul S.},\n\tmonth = nov,\n\tyear = {2018},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {10567--10569},\n\tfile = {Full Text PDF:files/1860/Chan et al. - 2018 - The 15th Anniversary of the U.S. National Nanotech.pdf:application/pdf;ACS Full Text Snapshot:files/1861/acsnano.html:text/html},\n}\n\n
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\n \n\n \n \n \n \n \n \n What Is the Value of Publishing?.\n \n \n \n \n\n\n \n Chan, W.\n\n\n \n\n\n\n ACS Nano, 12(7): 6345–6346. July 2018.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"WhatPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{chan_what_2018,\n\ttitle = {What {Is} the {Value} of {Publishing}?},\n\tvolume = {12},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.8b05296},\n\tdoi = {10.1021/acsnano.8b05296},\n\tnumber = {7},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Chan, Warren},\n\tmonth = jul,\n\tyear = {2018},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {6345--6346},\n\tfile = {Full Text PDF:files/1865/Chan - 2018 - What Is the Value of Publishing.pdf:application/pdf;ACS Full Text Snapshot:files/1868/acsnano.html:text/html},\n}\n\n
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\n \n\n \n \n \n \n \n \n Quantifying the Ligand-Coated Nanoparticle Delivery to Cancer Cells in Solid Tumors.\n \n \n \n \n\n\n \n Dai, Q., Wilhelm, S., Ding, D., Syed, A. M., Sindhwani, S., Zhang, Y., Chen, Y. Y., MacMillan, P., & Chan, W. C. W.\n\n\n \n\n\n\n ACS Nano, 12(8): 8423–8435. August 2018.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"QuantifyingPaper\n  \n \n \n \"Quantifying paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{dai_quantifying_2018,\n\ttitle = {Quantifying the {Ligand}-{Coated} {Nanoparticle} {Delivery} to {Cancer} {Cells} in {Solid} {Tumors}},\n\tvolume = {12},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.8b03900},\n\tdoi = {10.1021/acsnano.8b03900},\n\tabstract = {Coating the nanoparticle surface with cancer cell recognizing ligands is expected to facilitate specific delivery of nanoparticles to diseased cells in vivo. While this targeting strategy is appealing, no nanoparticle-based active targeting formulation for solid tumor treatment had made it past phase III clinical trials. Here, we quantified the cancer cell-targeting efficiencies of Trastuzumab (Herceptin) and folic acid coated gold and silica nanoparticles in multiple mouse tumor models. Surprisingly, we showed that less than 14 out of 1 million (0.0014\\% injected dose) intravenously administrated nanoparticles were delivered to targeted cancer cells, and that only 2 out of 100 cancer cells interacted with the nanoparticles. The majority of the intratumoral nanoparticles were either trapped in the extracellular matrix or taken up by perivascular tumor associated macrophages. The low cancer cell targeting efficiency and significant uptake by noncancer cells suggest the need to re-evaluate the active targeting process and therapeutic mechanisms using quantitative methods. This will be important for developing strategies to deliver emerging therapeutics such as genome editing, nucleic acid therapy, and immunotherapy for cancer treatment using nanocarriers.},\n\tnumber = {8},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Dai, Qin and Wilhelm, Stefan and Ding, Ding and Syed, Abdullah Muhammad and Sindhwani, Shrey and Zhang, Yuwei and Chen, Yih Yang and MacMillan, Presley and Chan, Warren C. W.},\n\tmonth = aug,\n\tyear = {2018},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {8423--8435},\n\tfile = {Full Text PDF:files/1867/Dai et al. - 2018 - Quantifying the Ligand-Coated Nanoparticle Deliver.pdf:application/pdf;ACS Full Text Snapshot:files/1871/acsnano.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acsnano.8b03900-min.pdf}\n}\n\n
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\n Coating the nanoparticle surface with cancer cell recognizing ligands is expected to facilitate specific delivery of nanoparticles to diseased cells in vivo. While this targeting strategy is appealing, no nanoparticle-based active targeting formulation for solid tumor treatment had made it past phase III clinical trials. Here, we quantified the cancer cell-targeting efficiencies of Trastuzumab (Herceptin) and folic acid coated gold and silica nanoparticles in multiple mouse tumor models. Surprisingly, we showed that less than 14 out of 1 million (0.0014% injected dose) intravenously administrated nanoparticles were delivered to targeted cancer cells, and that only 2 out of 100 cancer cells interacted with the nanoparticles. The majority of the intratumoral nanoparticles were either trapped in the extracellular matrix or taken up by perivascular tumor associated macrophages. The low cancer cell targeting efficiency and significant uptake by noncancer cells suggest the need to re-evaluate the active targeting process and therapeutic mechanisms using quantitative methods. This will be important for developing strategies to deliver emerging therapeutics such as genome editing, nucleic acid therapy, and immunotherapy for cancer treatment using nanocarriers.\n
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\n \n\n \n \n \n \n \n \n Helmuth Möhwald (1946–2018).\n \n \n \n \n\n\n \n Parak, W. J., Chan, W. W. C., Chhowalla, M., Farokhzad, O., Glotzer, S., Gogotsi, Y., Hammond, P. T., Hersam, M. C., Javey, A., Kagan, C. R., Kataoka, K., Khademhosseini, A., Kotov, N. A., Lee, S., Lee, Y. H., Li, Y., Millstone, J., Mulvaney, P. A., Nel, A. E., Nordlander, P. J., Penner, R. M., Rogach, A. L., Schaak, R. E., Stevens, M. M., Wee, A. T. S., Willson, C. G., & Weiss, P. S.\n\n\n \n\n\n\n ACS Nano, 12(4): 3053–3055. April 2018.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"HelmuthPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{parak_helmuth_2018,\n\ttitle = {Helmuth {Möhwald} (1946–2018)},\n\tvolume = {12},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.8b02755},\n\tdoi = {10.1021/acsnano.8b02755},\n\tnumber = {4},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Parak, Wolfgang J. and Chan, Warren W. C. and Chhowalla, Manish and Farokhzad, Omid and Glotzer, Sharon and Gogotsi, Yury and Hammond, Paula T. and Hersam, Mark C. and Javey, Ali and Kagan, Cherie R. and Kataoka, Kazunori and Khademhosseini, Ali and Kotov, Nicholas A. and Lee, Shuit-Tong and Lee, Young Hee and Li, Yan and Millstone, Jill and Mulvaney, Paul A. and Nel, Andre E. and Nordlander, Peter J. and Penner, Reginald M. and Rogach, Andrey L. and Schaak, Raymond E. and Stevens, Molly M. and Wee, Andrew T. S. and Willson, C. Grant and Weiss, Paul S.},\n\tmonth = apr,\n\tyear = {2018},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {3053--3055},\n\tfile = {Full Text PDF:files/1872/Parak et al. - 2018 - Helmuth Möhwald (1946–2018).pdf:application/pdf;ACS Full Text Snapshot:files/1875/acsnano.html:text/html},\n}\n\n
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\n  \n 2017\n \n \n (17)\n \n \n
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\n \n\n \n \n \n \n \n \n A Big Year Ahead for Nano in 2018.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n ACS Nano, 11(12): 11755–11757. December 2017.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"APaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{noauthor_big_2017,\n\ttitle = {A {Big} {Year} {Ahead} for {Nano} in 2018},\n\tvolume = {11},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.7b08851},\n\tdoi = {10.1021/acsnano.7b08851},\n\tnumber = {12},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tmonth = dec,\n\tyear = {2017},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {11755--11757},\n\tfile = {Full Text PDF:files/1874/2017 - A Big Year Ahead for Nano in 2018.pdf:application/pdf;ACS Full Text Snapshot:files/1880/acsnano.html:text/html},\n}\n\n
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\n \n\n \n \n \n \n \n \n Effect of removing Kupffer cells on nanoparticle tumor delivery.\n \n \n \n \n\n\n \n Tavares, A. J., Poon, W., Zhang, Y., Dai, Q., Besla, R., Ding, D., Ouyang, B., Li, A., Chen, J., Zheng, G., Robbins, C., & Chan, W. C. W.\n\n\n \n\n\n\n PNAS, 114(51): E10871–E10880. December 2017.\n Publisher: National Academy of Sciences Section: PNAS Plus\n\n\n\n
\n\n\n\n \n \n \"EffectPaper\n  \n \n \n \"Effect paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{tavares_effect_2017,\n\ttitle = {Effect of removing {Kupffer} cells on nanoparticle tumor delivery},\n\tvolume = {114},\n\tcopyright = {© 2017 . http://www.pnas.org.myaccess.library.utoronto.ca/site/aboutpnas/licenses.xhtmlPublished under the PNAS license.},\n\tissn = {0027-8424, 1091-6490},\n\turl = {http://www.pnas.org/content/114/51/E10871},\n\tdoi = {10.1073/pnas.1713390114},\n\tabstract = {A recent metaanalysis shows that 0.7\\% of nanoparticles are delivered to solid tumors. This low delivery efficiency has major implications in the translation of cancer nanomedicines, as most of the nanomedicines are sequestered by nontumor cells. To improve the delivery efficiency, there is a need to investigate the quantitative contribution of each organ in blocking the transport of nanoparticles to solid tumors. Here, we hypothesize that the removal of the liver macrophages, cells that have been reported to take up the largest amount of circulating nanoparticles, would lead to a significant increase in the nanoparticle delivery efficiency to solid tumors. We were surprised to discover that the maximum achievable delivery efficiency was only 2\\%. In our analysis, there was a clear correlation between particle design, chemical composition, macrophage depletion, tumor pathophysiology, and tumor delivery efficiency. In many cases, we observed an 18–150 times greater delivery efficiency, but we were not able to achieve a delivery efficiency higher than 2\\%. The results suggest the need to look deeper at other organs such as the spleen, lymph nodes, and tumor in mediating the delivery process. Systematically mapping the contribution of each organ quantitatively will allow us to pinpoint the cause of the low tumor delivery efficiency. This, in effect, enables the generation of a rational strategy to improve the delivery efficiency of nanoparticles to solid tumors either through the engineering of multifunctional nanosystems or through manipulation of biological barriers.},\n\tlanguage = {en},\n\tnumber = {51},\n\turldate = {2021-11-06},\n\tjournal = {PNAS},\n\tauthor = {Tavares, Anthony J. and Poon, Wilson and Zhang, Yi-Nan and Dai, Qin and Besla, Rickvinder and Ding, Ding and Ouyang, Ben and Li, Angela and Chen, Juan and Zheng, Gang and Robbins, Clinton and Chan, Warren C. W.},\n\tmonth = dec,\n\tyear = {2017},\n\tpmid = {29208719},\n\tnote = {Publisher: National Academy of Sciences\nSection: PNAS Plus},\n\tkeywords = {cancer, liver, macrophage, nanoparticle, tumor delivery},\n\tpages = {E10871--E10880},\n\tfile = {Full Text PDF:files/1877/Tavares et al. - 2017 - Effect of removing Kupffer cells on nanoparticle t.pdf:application/pdf;Snapshot:files/1881/E10871.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/E10871.full_.pdf}\n}\n\n
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\n A recent metaanalysis shows that 0.7% of nanoparticles are delivered to solid tumors. This low delivery efficiency has major implications in the translation of cancer nanomedicines, as most of the nanomedicines are sequestered by nontumor cells. To improve the delivery efficiency, there is a need to investigate the quantitative contribution of each organ in blocking the transport of nanoparticles to solid tumors. Here, we hypothesize that the removal of the liver macrophages, cells that have been reported to take up the largest amount of circulating nanoparticles, would lead to a significant increase in the nanoparticle delivery efficiency to solid tumors. We were surprised to discover that the maximum achievable delivery efficiency was only 2%. In our analysis, there was a clear correlation between particle design, chemical composition, macrophage depletion, tumor pathophysiology, and tumor delivery efficiency. In many cases, we observed an 18–150 times greater delivery efficiency, but we were not able to achieve a delivery efficiency higher than 2%. The results suggest the need to look deeper at other organs such as the spleen, lymph nodes, and tumor in mediating the delivery process. Systematically mapping the contribution of each organ quantitatively will allow us to pinpoint the cause of the low tumor delivery efficiency. This, in effect, enables the generation of a rational strategy to improve the delivery efficiency of nanoparticles to solid tumors either through the engineering of multifunctional nanosystems or through manipulation of biological barriers.\n
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\n \n\n \n \n \n \n \n \n The Role of Nanoparticle Design in Determining Analytical Performance of Lateral Flow Immunoassays.\n \n \n \n \n\n\n \n Zhan, L., Guo, S., Song, F., Gong, Y., Xu, F., Boulware, D. R., McAlpine, M. C., Chan, W. C. W., & Bischof, J. C.\n\n\n \n\n\n\n Nano Lett., 17(12): 7207–7212. December 2017.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"ThePaper\n  \n \n \n \"The paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{zhan_role_2017,\n\ttitle = {The {Role} of {Nanoparticle} {Design} in {Determining} {Analytical} {Performance} of {Lateral} {Flow} {Immunoassays}},\n\tvolume = {17},\n\tissn = {1530-6984},\n\turl = {https://doi.org/10.1021/acs.nanolett.7b02302},\n\tdoi = {10.1021/acs.nanolett.7b02302},\n\tabstract = {Rapid, simple, and cost-effective diagnostics are needed to improve healthcare at the point of care (POC). However, the most widely used POC diagnostic, the lateral flow immunoassay (LFA), is ∼1000-times less sensitive and has a smaller analytical range than laboratory tests, requiring a confirmatory test to establish truly negative results. Here, a rational and systematic strategy is used to design the LFA contrast label (i.e., gold nanoparticles) to improve the analytical sensitivity, analytical detection range, and antigen quantification of LFAs. Specifically, we discovered that the size (30, 60, or 100 nm) of the gold nanoparticles is a main contributor to the LFA analytical performance through both the degree of receptor interaction and the ultimate visual or thermal contrast signals. Using the optimal LFA design, we demonstrated the ability to improve the analytical sensitivity by 256-fold and expand the analytical detection range from 3 log10 to 6 log10 for diagnosing patients with inflammatory conditions by measuring C-reactive protein. This work demonstrates that, with appropriate design of the contrast label, a simple and commonly used diagnostic technology can compete with more expensive state-of-the-art laboratory tests.},\n\tnumber = {12},\n\turldate = {2021-11-06},\n\tjournal = {Nano Lett.},\n\tauthor = {Zhan, Li and Guo, Shuang-zhuang and Song, Fayi and Gong, Yan and Xu, Feng and Boulware, David R. and McAlpine, Michael C. and Chan, Warren C. W. and Bischof, John C.},\n\tmonth = dec,\n\tyear = {2017},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {7207--7212},\n\tfile = {Full Text PDF:files/1878/Zhan et al. - 2017 - The Role of Nanoparticle Design in Determining Ana.pdf:application/pdf;ACS Full Text Snapshot:files/1882/acs.nanolett.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acs.nanolett.7b02302.pdf}\n}\n\n
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\n Rapid, simple, and cost-effective diagnostics are needed to improve healthcare at the point of care (POC). However, the most widely used POC diagnostic, the lateral flow immunoassay (LFA), is ∼1000-times less sensitive and has a smaller analytical range than laboratory tests, requiring a confirmatory test to establish truly negative results. Here, a rational and systematic strategy is used to design the LFA contrast label (i.e., gold nanoparticles) to improve the analytical sensitivity, analytical detection range, and antigen quantification of LFAs. Specifically, we discovered that the size (30, 60, or 100 nm) of the gold nanoparticles is a main contributor to the LFA analytical performance through both the degree of receptor interaction and the ultimate visual or thermal contrast signals. Using the optimal LFA design, we demonstrated the ability to improve the analytical sensitivity by 256-fold and expand the analytical detection range from 3 log10 to 6 log10 for diagnosing patients with inflammatory conditions by measuring C-reactive protein. This work demonstrates that, with appropriate design of the contrast label, a simple and commonly used diagnostic technology can compete with more expensive state-of-the-art laboratory tests.\n
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\n \n\n \n \n \n \n \n \n Peptide–MHC-based nanomedicines for autoimmunity function as T-cell receptor microclustering devices.\n \n \n \n \n\n\n \n Singha, S., Shao, K., Yang, Y., Clemente-Casares, X., Solé, P., Clemente, A., Blanco, J., Dai, Q., Song, F., Liu, S. W., Yamanouchi, J., Umeshappa, C. S., Nanjundappa, R. H., Detampel, P., Amrein, M., Fandos, C., Tanguay, R., Newbigging, S., Serra, P., Khadra, A., Chan, W. C. W., & Santamaria, P.\n\n\n \n\n\n\n Nature Nanotech, 12(7): 701–710. July 2017.\n Bandiera_abtest: a Cg_type: Nature Research Journals Number: 7 Primary_atype: Research Publisher: Nature Publishing Group Subject_term: Biotechnology;Nanoparticles Subject_term_id: biotechnology;nanoparticles\n\n\n\n
\n\n\n\n \n \n \"Peptide–MHC-basedPaper\n  \n \n \n \"Peptide–MHC-based paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n\n\n\n
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@article{singha_peptidemhc-based_2017,\n\ttitle = {Peptide–{MHC}-based nanomedicines for autoimmunity function as {T}-cell receptor microclustering devices},\n\tvolume = {12},\n\tcopyright = {2017 Nature Publishing Group},\n\tissn = {1748-3395},\n\turl = {https://www.nature.com/articles/nnano.2017.56},\n\tdoi = {10.1038/nnano.2017.56},\n\tabstract = {We have shown that nanoparticles (NPs) can be used as ligand-multimerization platforms to activate specific cellular receptors in vivo. Nanoparticles coated with autoimmune disease-relevant peptide-major histocompatibility complexes (pMHC) blunted autoimmune responses by triggering the differentiation and expansion of antigen-specific regulatory T cells in vivo. Here, we define the engineering principles impacting biological activity, detail a synthesis process yielding safe and stable compounds, and visualize how these nanomedicines interact with cognate T cells. We find that the triggering properties of pMHC–NPs are a function of pMHC intermolecular distance and involve the sustained assembly of large antigen receptor microclusters on murine and human cognate T cells. These compounds show no off-target toxicity in zebrafish embryos, do not cause haematological, biochemical or histological abnormalities, and are rapidly captured by phagocytes or processed by the hepatobiliary system. This work lays the groundwork for the design of ligand-based NP formulations to re-program in vivo cellular responses using nanotechnology.},\n\tlanguage = {en},\n\tnumber = {7},\n\turldate = {2021-11-06},\n\tjournal = {Nature Nanotech},\n\tauthor = {Singha, Santiswarup and Shao, Kun and Yang, Yang and Clemente-Casares, Xavier and Solé, Patricia and Clemente, Antonio and Blanco, Jesús and Dai, Qin and Song, Fayi and Liu, Shang Wan and Yamanouchi, Jun and Umeshappa, Channakeshava Sokke and Nanjundappa, Roopa Hebbandi and Detampel, Pascal and Amrein, Matthias and Fandos, César and Tanguay, Robert and Newbigging, Susan and Serra, Pau and Khadra, Anmar and Chan, Warren C. W. and Santamaria, Pere},\n\tmonth = jul,\n\tyear = {2017},\n\tnote = {Bandiera\\_abtest: a\nCg\\_type: Nature Research Journals\nNumber: 7\nPrimary\\_atype: Research\nPublisher: Nature Publishing Group\nSubject\\_term: Biotechnology;Nanoparticles\nSubject\\_term\\_id: biotechnology;nanoparticles},\n\tkeywords = {Biotechnology, Nanoparticles},\n\tpages = {701--710},\n\tfile = {Full Text PDF:files/1885/Singha et al. - 2017 - Peptide–MHC-based nanomedicines for autoimmunity f.pdf:application/pdf;Snapshot:files/1887/nnano.2017.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2022/01/Singha-et-al.-2017-Peptide–MHC-based-nanomedicines-for-autoimmunity-f.pdf}\n}\n\n
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\n We have shown that nanoparticles (NPs) can be used as ligand-multimerization platforms to activate specific cellular receptors in vivo. Nanoparticles coated with autoimmune disease-relevant peptide-major histocompatibility complexes (pMHC) blunted autoimmune responses by triggering the differentiation and expansion of antigen-specific regulatory T cells in vivo. Here, we define the engineering principles impacting biological activity, detail a synthesis process yielding safe and stable compounds, and visualize how these nanomedicines interact with cognate T cells. We find that the triggering properties of pMHC–NPs are a function of pMHC intermolecular distance and involve the sustained assembly of large antigen receptor microclusters on murine and human cognate T cells. These compounds show no off-target toxicity in zebrafish embryos, do not cause haematological, biochemical or histological abnormalities, and are rapidly captured by phagocytes or processed by the hepatobiliary system. This work lays the groundwork for the design of ligand-based NP formulations to re-program in vivo cellular responses using nanotechnology.\n
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\n \n\n \n \n \n \n \n \n Three-Dimensional Imaging of Transparent Tissues via Metal Nanoparticle Labeling.\n \n \n \n \n\n\n \n Syed, A. M., Sindhwani, S., Wilhelm, S., Kingston, B. R., Lee, D. S. W., Gommerman, J. L., & Chan, W. C. W.\n\n\n \n\n\n\n J. Am. Chem. Soc., 139(29): 9961–9971. July 2017.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"Three-DimensionalPaper\n  \n \n \n \"Three-Dimensional paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{syed_three-dimensional_2017,\n\ttitle = {Three-{Dimensional} {Imaging} of {Transparent} {Tissues} via {Metal} {Nanoparticle} {Labeling}},\n\tvolume = {139},\n\tissn = {0002-7863},\n\turl = {https://doi.org/10.1021/jacs.7b04022},\n\tdoi = {10.1021/jacs.7b04022},\n\tabstract = {Chemical probes are key components of the bioimaging toolbox, as they label biomolecules in cells and tissues. The new challenge in bioimaging is to design chemical probes for three-dimensional (3D) tissue imaging. In this work, we discovered that light scattering of metal nanoparticles can provide 3D imaging contrast in intact and transparent tissues. The nanoparticles can act as a template for the chemical growth of a metal layer to further enhance the scattering signal. The use of chemically grown nanoparticles in whole tissues can amplify the scattering to produce a 1.4 million-fold greater photon yield than obtained using common fluorophores. These probes are non-photobleaching and can be used alongside fluorophores without interference. We demonstrated three distinct biomedical applications: (a) molecular imaging of blood vessels, (b) tracking of nanodrug carriers in tumors, and (c) mapping of lesions and immune cells in a multiple sclerosis mouse model. Our strategy establishes a distinct yet complementary set of imaging probes for understanding disease mechanisms in three dimensions.},\n\tnumber = {29},\n\turldate = {2021-11-06},\n\tjournal = {J. Am. Chem. Soc.},\n\tauthor = {Syed, Abdullah Muhammad and Sindhwani, Shrey and Wilhelm, Stefan and Kingston, Benjamin R. and Lee, Dennis S. W. and Gommerman, Jennifer L. and Chan, Warren C. W.},\n\tmonth = jul,\n\tyear = {2017},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {9961--9971},\n\tfile = {Full Text PDF:files/1886/Syed et al. - 2017 - Three-Dimensional Imaging of Transparent Tissues v.pdf:application/pdf;ACS Full Text Snapshot:files/1888/jacs.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2022/01/Syed-et-al.-2017-Three-Dimensional-Imaging-of-Transparent-Tissues-v.pdf}\n}\n\n
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\n Chemical probes are key components of the bioimaging toolbox, as they label biomolecules in cells and tissues. The new challenge in bioimaging is to design chemical probes for three-dimensional (3D) tissue imaging. In this work, we discovered that light scattering of metal nanoparticles can provide 3D imaging contrast in intact and transparent tissues. The nanoparticles can act as a template for the chemical growth of a metal layer to further enhance the scattering signal. The use of chemically grown nanoparticles in whole tissues can amplify the scattering to produce a 1.4 million-fold greater photon yield than obtained using common fluorophores. These probes are non-photobleaching and can be used alongside fluorophores without interference. We demonstrated three distinct biomedical applications: (a) molecular imaging of blood vessels, (b) tracking of nanodrug carriers in tumors, and (c) mapping of lesions and immune cells in a multiple sclerosis mouse model. Our strategy establishes a distinct yet complementary set of imaging probes for understanding disease mechanisms in three dimensions.\n
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\n \n\n \n \n \n \n \n \n Cancer: Nanoscience and Nanotechnology Approaches.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n ACS Nano, 11(5): 4375–4376. May 2017.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"Cancer:Paper\n  \n \n \n \"Cancer: paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{noauthor_cancer_2017,\n\ttitle = {Cancer: {Nanoscience} and {Nanotechnology} {Approaches}},\n\tvolume = {11},\n\tissn = {1936-0851},\n\tshorttitle = {Cancer},\n\turl = {https://doi.org/10.1021/acsnano.7b03308},\n\tdoi = {10.1021/acsnano.7b03308},\n\tnumber = {5},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tmonth = may,\n\tyear = {2017},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {4375--4376},\n\tfile = {Full Text PDF:files/1890/2017 - Cancer Nanoscience and Nanotechnology Approaches.pdf:application/pdf;ACS Full Text Snapshot:files/1894/acsnano.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acsnano.7b03308.pdf}\n}\n\n
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\n \n\n \n \n \n \n \n \n Making vessels more permeable.\n \n \n \n \n\n\n \n Syed, A. M., Sindhwani, S., & Chan, W. C. W.\n\n\n \n\n\n\n Nat Biomed Eng, 1(8): 629–631. August 2017.\n Bandiera_abtest: a Cg_type: Nature Research Journals Number: 8 Primary_atype: News & Views Publisher: Nature Publishing Group Subject_term: Cancer therapy;Nanomedicine;Platelets Subject_term_id: cancer-therapy;nanomedicine;platelets\n\n\n\n
\n\n\n\n \n \n \"MakingPaper\n  \n \n \n \"Making paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n\n\n\n
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@article{syed_making_2017,\n\ttitle = {Making vessels more permeable},\n\tvolume = {1},\n\tcopyright = {2017 The Publisher},\n\tissn = {2157-846X},\n\turl = {https://www.nature.com/articles/s41551-017-0123-8},\n\tdoi = {10.1038/s41551-017-0123-8},\n\tabstract = {Depletion of tumour-associated platelets improves the delivery of anticancer drugs.},\n\tlanguage = {en},\n\tnumber = {8},\n\turldate = {2021-11-06},\n\tjournal = {Nat Biomed Eng},\n\tauthor = {Syed, Abdullah Muhammad and Sindhwani, Shrey and Chan, Warren C. W.},\n\tmonth = aug,\n\tyear = {2017},\n\tnote = {Bandiera\\_abtest: a\nCg\\_type: Nature Research Journals\nNumber: 8\nPrimary\\_atype: News \\& Views\nPublisher: Nature Publishing Group\nSubject\\_term: Cancer therapy;Nanomedicine;Platelets\nSubject\\_term\\_id: cancer-therapy;nanomedicine;platelets},\n\tkeywords = {Cancer therapy, Nanomedicine, Platelets},\n\tpages = {629--631},\n\tfile = {Full Text PDF:files/1892/Syed et al. - 2017 - Making vessels more permeable.pdf:application/pdf;Snapshot:files/1893/s41551-017-0123-8.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2022/01/Syed-et-al.-2017-Making-vessels-more-permeable.pdf}\n}\n\n
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\n Depletion of tumour-associated platelets improves the delivery of anticancer drugs.\n
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\n \n\n \n \n \n \n \n \n Our First and Next Decades at ACS Nano.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n ACS Nano, 11(8): 7553–7555. August 2017.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"OurPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{noauthor_our_2017,\n\ttitle = {Our {First} and {Next} {Decades} at {ACS} {Nano}},\n\tvolume = {11},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.7b05765},\n\tdoi = {10.1021/acsnano.7b05765},\n\tnumber = {8},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tmonth = aug,\n\tyear = {2017},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {7553--7555},\n\tfile = {Full Text PDF:files/1896/2017 - Our First and Next Decades at ACS Nano.pdf:application/pdf;ACS Full Text Snapshot:files/1899/acsnano.html:text/html},\n}\n\n
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\n \n\n \n \n \n \n \n \n State of diagnosing infectious pathogens using colloidal nanomaterials.\n \n \n \n \n\n\n \n Kim, J., Mohamed, M. A. A., Zagorovsky, K., & Chan, W. C. W.\n\n\n \n\n\n\n Biomaterials, 146: 97–114. November 2017.\n \n\n\n\n
\n\n\n\n \n \n \"StatePaper\n  \n \n \n \"State paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{kim_state_2017,\n\ttitle = {State of diagnosing infectious pathogens using colloidal nanomaterials},\n\tvolume = {146},\n\tissn = {0142-9612},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0142961217305239},\n\tdoi = {10.1016/j.biomaterials.2017.08.013},\n\tabstract = {Infectious diseases are a major global threat that accounts for one of the leading causes of global mortality and morbidity. Prompt diagnosis is a crucial first step in the management of infectious threats, which aims to quarantine infected patients to avoid contacts with healthy individuals and deliver effective treatments prior to further spread of diseases. This review article discusses current advances of diagnostic systems using colloidal nanomaterials (e.g., gold nanoparticles, quantum dots, magnetic nanoparticles) for identifying and differentiating infectious pathogens. The challenges involved in the clinical translation of these emerging nanotechnology based diagnostic devices will also be discussed.},\n\tlanguage = {en},\n\turldate = {2021-11-06},\n\tjournal = {Biomaterials},\n\tauthor = {Kim, Jisung and Mohamed, Mohamed A. Abdou and Zagorovsky, Kyryl and Chan, Warren C. W.},\n\tmonth = nov,\n\tyear = {2017},\n\tkeywords = {Clinical translation, Diagnostics, Nanomaterials, Nanotechnology, Point of care},\n\tpages = {97--114},\n\tfile = {ScienceDirect Full Text PDF:files/1898/Kim et al. - 2017 - State of diagnosing infectious pathogens using col.pdf:application/pdf},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/1-s2.0-S0142961217305239-main-min.pdf}\n}\n\n
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\n Infectious diseases are a major global threat that accounts for one of the leading causes of global mortality and morbidity. Prompt diagnosis is a crucial first step in the management of infectious threats, which aims to quarantine infected patients to avoid contacts with healthy individuals and deliver effective treatments prior to further spread of diseases. This review article discusses current advances of diagnostic systems using colloidal nanomaterials (e.g., gold nanoparticles, quantum dots, magnetic nanoparticles) for identifying and differentiating infectious pathogens. The challenges involved in the clinical translation of these emerging nanotechnology based diagnostic devices will also be discussed.\n
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\n \n\n \n \n \n \n \n \n Simplifying Assays by Tableting Reagents.\n \n \n \n \n\n\n \n Udugama, B., Kadhiresan, P., Samarakoon, A., & Chan, W. C. W.\n\n\n \n\n\n\n J. Am. Chem. Soc., 139(48): 17341–17349. December 2017.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"SimplifyingPaper\n  \n \n \n \"Simplifying paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{udugama_simplifying_2017,\n\ttitle = {Simplifying {Assays} by {Tableting} {Reagents}},\n\tvolume = {139},\n\tissn = {0002-7863},\n\turl = {https://doi.org/10.1021/jacs.7b07055},\n\tdoi = {10.1021/jacs.7b07055},\n\tabstract = {Medical diagnostic assays provide exquisite sensitivity and precision in the diagnoses of patients. However, these technologies often require multiple steps, skilled technicians, and facilities to store heat-sensitive reagents. Here, we developed a high-throughput compression method to incorporate different assay components into color-coded tablets. With our technique, premeasured quantities of reagents can be encapsulated in compressed tablets. We show that tableting stabilizes heat-sensitive reagents and simplifies a broad range of assays, including isothermal nucleic acid amplification techniques, enzyme-based immunoassays, and microbead diagnostics. To test the clinical readiness of this tableting technology, we show the ability of tableted diagnostics for screening hepatitis B-positive patient samples. Our development simplifies complicated assays and the transportation of reagents and mitigates the need for refrigeration of reagents. This advances the use of complex assays in remote areas with limited infrastructure.},\n\tnumber = {48},\n\turldate = {2021-11-06},\n\tjournal = {J. Am. Chem. Soc.},\n\tauthor = {Udugama, Buddhisha and Kadhiresan, Pranav and Samarakoon, Amila and Chan, Warren C. W.},\n\tmonth = dec,\n\tyear = {2017},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {17341--17349},\n\tfile = {Full Text PDF:files/1901/Udugama et al. - 2017 - Simplifying Assays by Tableting Reagents.pdf:application/pdf;ACS Full Text Snapshot:files/1902/jacs.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/jacs.7b07055-min.pdf}\n}\n\n
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\n Medical diagnostic assays provide exquisite sensitivity and precision in the diagnoses of patients. However, these technologies often require multiple steps, skilled technicians, and facilities to store heat-sensitive reagents. Here, we developed a high-throughput compression method to incorporate different assay components into color-coded tablets. With our technique, premeasured quantities of reagents can be encapsulated in compressed tablets. We show that tableting stabilizes heat-sensitive reagents and simplifies a broad range of assays, including isothermal nucleic acid amplification techniques, enzyme-based immunoassays, and microbead diagnostics. To test the clinical readiness of this tableting technology, we show the ability of tableted diagnostics for screening hepatitis B-positive patient samples. Our development simplifies complicated assays and the transportation of reagents and mitigates the need for refrigeration of reagents. This advances the use of complex assays in remote areas with limited infrastructure.\n
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\n \n\n \n \n \n \n \n \n Nanoscience and Nanotechnology Cross Borders.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n ACS Nano, 11(2): 1123–1126. February 2017.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"NanosciencePaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{noauthor_nanoscience_2017,\n\ttitle = {Nanoscience and {Nanotechnology} {Cross} {Borders}},\n\tvolume = {11},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.7b00953},\n\tdoi = {10.1021/acsnano.7b00953},\n\tnumber = {2},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tmonth = feb,\n\tyear = {2017},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {1123--1126},\n\tfile = {Full Text PDF:files/1904/2017 - Nanoscience and Nanotechnology Cross Borders.pdf:application/pdf;ACS Full Text Snapshot:files/1908/acsnano.html:text/html},\n}\n\n
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\n \n\n \n \n \n \n \n \n Nanomedicine 2.0.\n \n \n \n \n\n\n \n Chan, W. C. W.\n\n\n \n\n\n\n Acc. Chem. Res., 50(3): 627–632. March 2017.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"NanomedicinePaper\n  \n \n \n \"Nanomedicine paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{chan_nanomedicine_2017,\n\ttitle = {Nanomedicine 2.0},\n\tvolume = {50},\n\tissn = {0001-4842},\n\turl = {https://doi.org/10.1021/acs.accounts.6b00629},\n\tdoi = {10.1021/acs.accounts.6b00629},\n\tabstract = {Nanotechnology can profoundly change the way we diagnose and treat diseases, but the ability to control how engineered nanoparticles behave within the body remains largely elusive. This Commentary describes the progress and limitations of nanomedicine and the research and experimental philosophies that should be considered in our quest to advance nanotechnology to the clinic.},\n\tnumber = {3},\n\turldate = {2021-11-06},\n\tjournal = {Acc. Chem. Res.},\n\tauthor = {Chan, Warren C. W.},\n\tmonth = mar,\n\tyear = {2017},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {627--632},\n\tfile = {Full Text PDF:files/1906/Chan - 2017 - Nanomedicine 2.0.pdf:application/pdf;ACS Full Text Snapshot:files/1912/acs.accounts.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acs.accounts.6b00629-min.pdf}\n}\n\n
\n
\n\n\n
\n Nanotechnology can profoundly change the way we diagnose and treat diseases, but the ability to control how engineered nanoparticles behave within the body remains largely elusive. This Commentary describes the progress and limitations of nanomedicine and the research and experimental philosophies that should be considered in our quest to advance nanotechnology to the clinic.\n
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\n \n\n \n \n \n \n \n \n Diverse Applications of Nanomedicine.\n \n \n \n \n\n\n \n Pelaz, B., Alexiou, C., Alvarez-Puebla, R. A., Alves, F., Andrews, A. M., Ashraf, S., Balogh, L. P., Ballerini, L., Bestetti, A., Brendel, C., Bosi, S., Carril, M., Chan, W. C. W., Chen, C., Chen, X., Chen, X., Cheng, Z., Cui, D., Du, J., Dullin, C., Escudero, A., Feliu, N., Gao, M., George, M., Gogotsi, Y., Grünweller, A., Gu, Z., Halas, N. J., Hampp, N., Hartmann, R. K., Hersam, M. C., Hunziker, P., Jian, J., Jiang, X., Jungebluth, P., Kadhiresan, P., Kataoka, K., Khademhosseini, A., Kopeček, J., Kotov, N. A., Krug, H. F., Lee, D. S., Lehr, C., Leong, K. W., Liang, X., Ling Lim, M., Liz-Marzán, L. M., Ma, X., Macchiarini, P., Meng, H., Möhwald, H., Mulvaney, P., Nel, A. E., Nie, S., Nordlander, P., Okano, T., Oliveira, J., Park, T. H., Penner, R. M., Prato, M., Puntes, V., Rotello, V. M., Samarakoon, A., Schaak, R. E., Shen, Y., Sjöqvist, S., Skirtach, A. G., Soliman, M. G., Stevens, M. M., Sung, H., Tang, B. Z., Tietze, R., Udugama, B. N., VanEpps, J. S., Weil, T., Weiss, P. S., Willner, I., Wu, Y., Yang, L., Yue, Z., Zhang, Q., Zhang, Q., Zhang, X., Zhao, Y., Zhou, X., & Parak, W. J.\n\n\n \n\n\n\n ACS Nano, 11(3): 2313–2381. March 2017.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"DiversePaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{pelaz_diverse_2017,\n\ttitle = {Diverse {Applications} of {Nanomedicine}},\n\tvolume = {11},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.6b06040},\n\tdoi = {10.1021/acsnano.6b06040},\n\tabstract = {The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.},\n\tnumber = {3},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Pelaz, Beatriz and Alexiou, Christoph and Alvarez-Puebla, Ramon A. and Alves, Frauke and Andrews, Anne M. and Ashraf, Sumaira and Balogh, Lajos P. and Ballerini, Laura and Bestetti, Alessandra and Brendel, Cornelia and Bosi, Susanna and Carril, Monica and Chan, Warren C. W. and Chen, Chunying and Chen, Xiaodong and Chen, Xiaoyuan and Cheng, Zhen and Cui, Daxiang and Du, Jianzhong and Dullin, Christian and Escudero, Alberto and Feliu, Neus and Gao, Mingyuan and George, Michael and Gogotsi, Yury and Grünweller, Arnold and Gu, Zhongwei and Halas, Naomi J. and Hampp, Norbert and Hartmann, Roland K. and Hersam, Mark C. and Hunziker, Patrick and Jian, Ji and Jiang, Xingyu and Jungebluth, Philipp and Kadhiresan, Pranav and Kataoka, Kazunori and Khademhosseini, Ali and Kopeček, Jindřich and Kotov, Nicholas A. and Krug, Harald F. and Lee, Dong Soo and Lehr, Claus-Michael and Leong, Kam W. and Liang, Xing-Jie and Ling Lim, Mei and Liz-Marzán, Luis M. and Ma, Xiaowei and Macchiarini, Paolo and Meng, Huan and Möhwald, Helmuth and Mulvaney, Paul and Nel, Andre E. and Nie, Shuming and Nordlander, Peter and Okano, Teruo and Oliveira, Jose and Park, Tai Hyun and Penner, Reginald M. and Prato, Maurizio and Puntes, Victor and Rotello, Vincent M. and Samarakoon, Amila and Schaak, Raymond E. and Shen, Youqing and Sjöqvist, Sebastian and Skirtach, Andre G. and Soliman, Mahmoud G. and Stevens, Molly M. and Sung, Hsing-Wen and Tang, Ben Zhong and Tietze, Rainer and Udugama, Buddhisha N. and VanEpps, J. Scott and Weil, Tanja and Weiss, Paul S. and Willner, Itamar and Wu, Yuzhou and Yang, Lily and Yue, Zhao and Zhang, Qian and Zhang, Qiang and Zhang, Xian-En and Zhao, Yuliang and Zhou, Xin and Parak, Wolfgang J.},\n\tmonth = mar,\n\tyear = {2017},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {2313--2381},\n\tfile = {Full Text PDF:files/1910/Pelaz et al. - 2017 - Diverse Applications of Nanomedicine.pdf:application/pdf},\n}\n\n
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\n The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.\n
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\n \n\n \n \n \n \n \n \n Phenotype Determines Nanoparticle Uptake by Human Macrophages from Liver and Blood.\n \n \n \n \n\n\n \n MacParland, S. A., Tsoi, K. M., Ouyang, B., Ma, X., Manuel, J., Fawaz, A., Ostrowski, M. A., Alman, B. A., Zilman, A., Chan, W. C., & McGilvray, I. D.\n\n\n \n\n\n\n ACS Nano, 11(3): 2428–2443. March 2017.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"PhenotypePaper\n  \n \n \n \"Phenotype paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{macparland_phenotype_2017,\n\ttitle = {Phenotype {Determines} {Nanoparticle} {Uptake} by {Human} {Macrophages} from {Liver} and {Blood}},\n\tvolume = {11},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.6b06245},\n\tdoi = {10.1021/acsnano.6b06245},\n\tabstract = {A significant challenge to delivering therapeutic doses of nanoparticles to targeted disease sites is the fact that most nanoparticles become trapped in the liver. Liver-resident macrophages, or Kupffer cells, are key cells in the hepatic sequestration of nanoparticles. However, the precise role that the macrophage phenotype plays in nanoparticle uptake is unknown. Here, we show that the human macrophage phenotype modulates hard nanoparticle uptake. Using gold nanoparticles, we examined uptake by human monocyte-derived macrophages that had been driven to a “regulatory” M2 phenotype or an “inflammatory” M1 phenotype and found that M2-type macrophages preferentially take up nanoparticles, with a clear hierarchy among the subtypes (M2c {\\textgreater} M2 {\\textgreater} M2a {\\textgreater} M2b {\\textgreater} M1). We also found that stimuli such as LPS/IFN-γ rather than with more “regulatory” stimuli such as TGF-β/IL-10 reduce per cell macrophage nanoparticle uptake by an average of 40\\%. Primary human Kupffer cells were found to display heterogeneous expression of M1 and M2 markers, and Kupffer cells expressing higher levels of M2 markers (CD163) take up significantly more nanoparticles than Kupffer cells expressing lower levels of surface CD163. Our results demonstrate that hepatic inflammatory microenvironments should be considered when studying liver sequestration of nanoparticles, and that modifying the hepatic microenvironment might offer a tool for enhancing or decreasing this sequestration. Our findings also suggest that models examining the nanoparticle/macrophage interaction should include studies with primary tissue macrophages.},\n\tnumber = {3},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {MacParland, Sonya A. and Tsoi, Kim M. and Ouyang, Ben and Ma, Xue-Zhong and Manuel, Justin and Fawaz, Ali and Ostrowski, Mario A. and Alman, Benjamin A. and Zilman, Anton and Chan, Warren C.W. and McGilvray, Ian D.},\n\tmonth = mar,\n\tyear = {2017},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {2428--2443},\n\tfile = {Full Text PDF:files/1914/MacParland et al. - 2017 - Phenotype Determines Nanoparticle Uptake by Human .pdf:application/pdf;ACS Full Text Snapshot:files/1918/acsnano.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acsnano.6b06245-min.pdf}\n}\n\n
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\n A significant challenge to delivering therapeutic doses of nanoparticles to targeted disease sites is the fact that most nanoparticles become trapped in the liver. Liver-resident macrophages, or Kupffer cells, are key cells in the hepatic sequestration of nanoparticles. However, the precise role that the macrophage phenotype plays in nanoparticle uptake is unknown. Here, we show that the human macrophage phenotype modulates hard nanoparticle uptake. Using gold nanoparticles, we examined uptake by human monocyte-derived macrophages that had been driven to a “regulatory” M2 phenotype or an “inflammatory” M1 phenotype and found that M2-type macrophages preferentially take up nanoparticles, with a clear hierarchy among the subtypes (M2c \\textgreater M2 \\textgreater M2a \\textgreater M2b \\textgreater M1). We also found that stimuli such as LPS/IFN-γ rather than with more “regulatory” stimuli such as TGF-β/IL-10 reduce per cell macrophage nanoparticle uptake by an average of 40%. Primary human Kupffer cells were found to display heterogeneous expression of M1 and M2 markers, and Kupffer cells expressing higher levels of M2 markers (CD163) take up significantly more nanoparticles than Kupffer cells expressing lower levels of surface CD163. Our results demonstrate that hepatic inflammatory microenvironments should be considered when studying liver sequestration of nanoparticles, and that modifying the hepatic microenvironment might offer a tool for enhancing or decreasing this sequestration. Our findings also suggest that models examining the nanoparticle/macrophage interaction should include studies with primary tissue macrophages.\n
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\n \n\n \n \n \n \n \n \n Yeast Populations Evolve to Resist CdSe Quantum Dot Toxicity.\n \n \n \n \n\n\n \n Strtak, A., Sathiamoorthy, S., Tang, P. S., Tsoi, K. M., Song, F., Anderson, J. B., Chan, W. C. W., & Shin, J. A.\n\n\n \n\n\n\n Bioconjugate Chem., 28(4): 1205–1213. April 2017.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"YeastPaper\n  \n \n \n \"Yeast paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{strtak_yeast_2017,\n\ttitle = {Yeast {Populations} {Evolve} to {Resist} {CdSe} {Quantum} {Dot} {Toxicity}},\n\tvolume = {28},\n\tissn = {1043-1802},\n\turl = {https://doi.org/10.1021/acs.bioconjchem.7b00056},\n\tdoi = {10.1021/acs.bioconjchem.7b00056},\n\tabstract = {Engineered nanomaterials are used globally in biomedical, electronic, and optical devices, and are often discarded into the environment. Cell culture experiments have shown that many inorganic nanoparticles are toxic to eukaryotic cells. Here, we show that populations of eukaryotic cells can evolve to survive chronic exposure to toxic CdSe semiconductor quantum dots (QDs). We grew yeast Saccharomyces cerevisiae for 24 days in liquid medium containing QDs prepared daily at half the minimum inhibitory concentration (MIC50) of the progenitor yeast cells. After 24 days, the cells grew normally under constant exposure to QDs. We concluded that these cells evolved to resist QD toxicity. Surprisingly, when we removed QDs from the growth medium, some of the evolved cells grew poorly, i.e., they grew better in the presence of QDs. Finally, genetic analysis confirmed that the ubiquitin ligase gene bul1 was mutated in the evolved cells, which suggests that this gene may be implicated in increased CdSe QD tolerance. This study shows that chronic exposure to QDs can exert selective pressure causing irreversible genetic changes leading to adaptation.},\n\tnumber = {4},\n\turldate = {2021-11-06},\n\tjournal = {Bioconjugate Chem.},\n\tauthor = {Strtak, Alexandra and Sathiamoorthy, Sarmitha and Tang, Peter S. and Tsoi, Kim M. and Song, Fayi and Anderson, James B. and Chan, Warren C. W. and Shin, Jumi A.},\n\tmonth = apr,\n\tyear = {2017},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {1205--1213},\n\tfile = {Full Text PDF:files/1915/Strtak et al. - 2017 - Yeast Populations Evolve to Resist CdSe Quantum Do.pdf:application/pdf;ACS Full Text Snapshot:files/1919/acs.bioconjchem.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acs.bioconjchem.7b00056-min.pdf}\n}\n\n
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\n Engineered nanomaterials are used globally in biomedical, electronic, and optical devices, and are often discarded into the environment. Cell culture experiments have shown that many inorganic nanoparticles are toxic to eukaryotic cells. Here, we show that populations of eukaryotic cells can evolve to survive chronic exposure to toxic CdSe semiconductor quantum dots (QDs). We grew yeast Saccharomyces cerevisiae for 24 days in liquid medium containing QDs prepared daily at half the minimum inhibitory concentration (MIC50) of the progenitor yeast cells. After 24 days, the cells grew normally under constant exposure to QDs. We concluded that these cells evolved to resist QD toxicity. Surprisingly, when we removed QDs from the growth medium, some of the evolved cells grew poorly, i.e., they grew better in the presence of QDs. Finally, genetic analysis confirmed that the ubiquitin ligase gene bul1 was mutated in the evolved cells, which suggests that this gene may be implicated in increased CdSe QD tolerance. This study shows that chronic exposure to QDs can exert selective pressure causing irreversible genetic changes leading to adaptation.\n
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\n \n\n \n \n \n \n \n \n Accelerating Advances in Science, Engineering, and Medicine through Nanoscience and Nanotechnology.\n \n \n \n \n\n\n \n Chan, W. C. W., Khademhosseini, A., Möhwald, H., Parak, W. J., Miller, J. F., Ozcan, A., & Weiss, P. S.\n\n\n \n\n\n\n ACS Nano, 11(4): 3423–3424. April 2017.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"AcceleratingPaper\n  \n \n \n \"Accelerating paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{chan_accelerating_2017,\n\ttitle = {Accelerating {Advances} in {Science}, {Engineering}, and {Medicine} through {Nanoscience} and {Nanotechnology}},\n\tvolume = {11},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.7b02616},\n\tdoi = {10.1021/acsnano.7b02616},\n\tnumber = {4},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Chan, Warren C. W. and Khademhosseini, Ali and Möhwald, Helmuth and Parak, Wolfgang J. and Miller, Jeff F. and Ozcan, Aydogan and Weiss, Paul S.},\n\tmonth = apr,\n\tyear = {2017},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {3423--3424},\n\tfile = {Full Text PDF:files/1916/Chan et al. - 2017 - Accelerating Advances in Science, Engineering, and.pdf:application/pdf;ACS Full Text Snapshot:files/1917/acsnano.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acsnano.7b02616.pdf}\n}\n\n
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\n \n\n \n \n \n \n \n \n Exploring Passive Clearing for 3D Optical Imaging of Nanoparticles in Intact Tissues.\n \n \n \n \n\n\n \n Sindhwani, S., Syed, A. M., Wilhelm, S., & Chan, W. C. W.\n\n\n \n\n\n\n Bioconjugate Chem., 28(1): 253–259. January 2017.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"ExploringPaper\n  \n \n \n \"Exploring paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{sindhwani_exploring_2017,\n\ttitle = {Exploring {Passive} {Clearing} for {3D} {Optical} {Imaging} of {Nanoparticles} in {Intact} {Tissues}},\n\tvolume = {28},\n\tissn = {1043-1802},\n\turl = {https://doi.org/10.1021/acs.bioconjchem.6b00500},\n\tdoi = {10.1021/acs.bioconjchem.6b00500},\n\tabstract = {The three-dimensional (3D) optical imaging of nanoparticle distribution within cells and tissues can provide insights into barriers to nanoparticle transport in vivo. However, this approach requires the preparation of optically transparent samples using harsh chemical and physical methods, which can lead to a significant loss of nanoparticles and decreased sensitivity of subsequent analyses. Here, we investigate the influence of electrophoresis and clearing time on nanoparticle retention within intact tissues and the impact of these factors on the final 3D image quality. Our findings reveal that longer clearing times lead to a loss of nanoparticles but improved transparency of tissues. We discovered that passive clearing improved nanoparticle retention 2-fold compared to results from electrophoretic clearing. Using the passive clearing approach, we were able to observe a small population of nanoparticles undergoing hepatobiliary clearance, which could not be observed in liver tissues that were prepared by electrophoretic clearing. This strategy enables researchers to visualize the interface between nanomaterials and their surrounding biological environment with high sensitivity, which enables quantitative and unbiased analysis for guiding the next generation of nanomedicine designs.},\n\tnumber = {1},\n\turldate = {2021-11-06},\n\tjournal = {Bioconjugate Chem.},\n\tauthor = {Sindhwani, Shrey and Syed, Abdullah Muhammad and Wilhelm, Stefan and Chan, Warren C. W.},\n\tmonth = jan,\n\tyear = {2017},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {253--259},\n\tfile = {Full Text PDF:files/1924/Sindhwani et al. - 2017 - Exploring Passive Clearing for 3D Optical Imaging .pdf:application/pdf;ACS Full Text Snapshot:files/1926/acs.bioconjchem.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acs.bioconjchem.6b00500-min.pdf}\n}\n\n
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\n The three-dimensional (3D) optical imaging of nanoparticle distribution within cells and tissues can provide insights into barriers to nanoparticle transport in vivo. However, this approach requires the preparation of optically transparent samples using harsh chemical and physical methods, which can lead to a significant loss of nanoparticles and decreased sensitivity of subsequent analyses. Here, we investigate the influence of electrophoresis and clearing time on nanoparticle retention within intact tissues and the impact of these factors on the final 3D image quality. Our findings reveal that longer clearing times lead to a loss of nanoparticles but improved transparency of tissues. We discovered that passive clearing improved nanoparticle retention 2-fold compared to results from electrophoretic clearing. Using the passive clearing approach, we were able to observe a small population of nanoparticles undergoing hepatobiliary clearance, which could not be observed in liver tissues that were prepared by electrophoretic clearing. This strategy enables researchers to visualize the interface between nanomaterials and their surrounding biological environment with high sensitivity, which enables quantitative and unbiased analysis for guiding the next generation of nanomedicine designs.\n
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\n  \n 2016\n \n \n (19)\n \n \n
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\n \n\n \n \n \n \n \n \n Clarifying intact 3D tissues on a microfluidic chip for high-throughput structural analysis.\n \n \n \n \n\n\n \n Chen, Y. Y., Silva, P. N., Syed, A. M., Sindhwani, S., Rocheleau, J. V., & Chan, W. C. W.\n\n\n \n\n\n\n PNAS, 113(52): 14915–14920. December 2016.\n Publisher: National Academy of Sciences Section: Physical Sciences\n\n\n\n
\n\n\n\n \n \n \"ClarifyingPaper\n  \n \n \n \"Clarifying paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{chen_clarifying_2016,\n\ttitle = {Clarifying intact {3D} tissues on a microfluidic chip for high-throughput structural analysis},\n\tvolume = {113},\n\tcopyright = {©  . http://www.pnas.org.myaccess.library.utoronto.ca/site/misc/userlicense.xhtml},\n\tissn = {0027-8424, 1091-6490},\n\turl = {http://www.pnas.org/content/113/52/14915},\n\tdoi = {10.1073/pnas.1609569114},\n\tabstract = {On-chip imaging of intact three-dimensional tissues within microfluidic devices is fundamentally hindered by intratissue optical scattering, which impedes their use as tissue models for high-throughput screening assays. Here, we engineered a microfluidic system that preserves and converts tissues into optically transparent structures in less than 1 d, which is 20× faster than current passive clearing approaches. Accelerated clearing was achieved because the microfluidic system enhanced the exchange of interstitial fluids by 567-fold, which increased the rate of removal of optically scattering lipid molecules from the cross-linked tissue. Our enhanced clearing process allowed us to fluorescently image and map the segregation and compartmentalization of different cells during the formation of tumor spheroids, and to track the degradation of vasculature over time within extracted murine pancreatic islets in static culture, which may have implications on the efficacy of beta-cell transplantation treatments for type 1 diabetes. We further developed an image analysis algorithm that automates the analysis of the vasculature connectivity, volume, and cellular spatial distribution of the intact tissue. Our technique allows whole tissue analysis in microfluidic systems, and has implications in the development of organ-on-a-chip systems, high-throughput drug screening devices, and in regenerative medicine.},\n\tlanguage = {en},\n\tnumber = {52},\n\turldate = {2021-11-06},\n\tjournal = {PNAS},\n\tauthor = {Chen, Yih Yang and Silva, Pamuditha N. and Syed, Abdullah Muhammad and Sindhwani, Shrey and Rocheleau, Jonathan V. and Chan, Warren C. W.},\n\tmonth = dec,\n\tyear = {2016},\n\tpmid = {27956625},\n\tnote = {Publisher: National Academy of Sciences\nSection: Physical Sciences},\n\tkeywords = {3D imaging, CLARITY, computational analysis, fluorescence imaging, microfluidic},\n\tpages = {14915--14920},\n\tfile = {Full Text PDF:files/1921/Chen et al. - 2016 - Clarifying intact 3D tissues on a microfluidic chi.pdf:application/pdf;Snapshot:files/1925/14915.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/14915.full_.pdf}\n}\n\n
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\n On-chip imaging of intact three-dimensional tissues within microfluidic devices is fundamentally hindered by intratissue optical scattering, which impedes their use as tissue models for high-throughput screening assays. Here, we engineered a microfluidic system that preserves and converts tissues into optically transparent structures in less than 1 d, which is 20× faster than current passive clearing approaches. Accelerated clearing was achieved because the microfluidic system enhanced the exchange of interstitial fluids by 567-fold, which increased the rate of removal of optically scattering lipid molecules from the cross-linked tissue. Our enhanced clearing process allowed us to fluorescently image and map the segregation and compartmentalization of different cells during the formation of tumor spheroids, and to track the degradation of vasculature over time within extracted murine pancreatic islets in static culture, which may have implications on the efficacy of beta-cell transplantation treatments for type 1 diabetes. We further developed an image analysis algorithm that automates the analysis of the vasculature connectivity, volume, and cellular spatial distribution of the intact tissue. Our technique allows whole tissue analysis in microfluidic systems, and has implications in the development of organ-on-a-chip systems, high-throughput drug screening devices, and in regenerative medicine.\n
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\n \n\n \n \n \n \n \n \n Thermal Contrast Amplification Reader Yielding 8-Fold Analytical Improvement for Disease Detection with Lateral Flow Assays.\n \n \n \n \n\n\n \n Wang, Y., Qin, Z., Boulware, D. R., Pritt, B. S., Sloan, L. M., González, I. J., Bell, D., Rees-Channer, R. R., Chiodini, P., Chan, W. C. W., & Bischof, J. C.\n\n\n \n\n\n\n Anal. Chem., 88(23): 11774–11782. December 2016.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"ThermalPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{wang_thermal_2016,\n\ttitle = {Thermal {Contrast} {Amplification} {Reader} {Yielding} 8-{Fold} {Analytical} {Improvement} for {Disease} {Detection} with {Lateral} {Flow} {Assays}},\n\tvolume = {88},\n\tissn = {0003-2700},\n\turl = {https://doi.org/10.1021/acs.analchem.6b03406},\n\tdoi = {10.1021/acs.analchem.6b03406},\n\tabstract = {There is an increasing need for highly sensitive and quantitative diagnostics at the point-of-care. The lateral flow immunoassay (LFA) is one of the most widely used point-of-care diagnostic tests; however, LFAs generally suffer from low sensitivity and lack of quantification. To overcome these limitations, thermal contrast amplification (TCA) is a new method that is based on the laser excitation of gold nanoparticles (GNPs), the most commonly used visual signature, to evoke a thermal signature. To facilitate the clinical translation of the TCA technology, we present the development of a TCA reader, a platform technology that significantly improves the limit of detection and provides quantification of disease antigens in LFAs. This TCA reader provides enhanced sensitivity over visual detection by the human eye or by a colorimetric reader (e.g., BD Veritor System Reader). More specifically, the TCA reader demonstrated up to an 8-fold enhanced analytical sensitivity and quantification among LFAs for influenza, malaria, and Clostridium difficile. Systematic characterization of the laser, infrared camera, and other components of the reader and their integration into a working reader instrument are described. The development of the TCA reader enables simple, highly sensitive quantification of LFAs at the point-of-care.},\n\tnumber = {23},\n\turldate = {2021-11-06},\n\tjournal = {Anal. Chem.},\n\tauthor = {Wang, Yiru and Qin, Zhenpeng and Boulware, David R. and Pritt, Bobbi S. and Sloan, Lynne M. and González, Iveth J. and Bell, David and Rees-Channer, Roxanne R. and Chiodini, Peter and Chan, Warren C. W. and Bischof, John C.},\n\tmonth = dec,\n\tyear = {2016},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {11774--11782},\n\tfile = {Full Text PDF:files/1932/Wang et al. - 2016 - Thermal Contrast Amplification Reader Yielding 8-F.pdf:application/pdf;ACS Full Text Snapshot:files/1936/acs.analchem.html:text/html},\n}\n\n
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\n There is an increasing need for highly sensitive and quantitative diagnostics at the point-of-care. The lateral flow immunoassay (LFA) is one of the most widely used point-of-care diagnostic tests; however, LFAs generally suffer from low sensitivity and lack of quantification. To overcome these limitations, thermal contrast amplification (TCA) is a new method that is based on the laser excitation of gold nanoparticles (GNPs), the most commonly used visual signature, to evoke a thermal signature. To facilitate the clinical translation of the TCA technology, we present the development of a TCA reader, a platform technology that significantly improves the limit of detection and provides quantification of disease antigens in LFAs. This TCA reader provides enhanced sensitivity over visual detection by the human eye or by a colorimetric reader (e.g., BD Veritor System Reader). More specifically, the TCA reader demonstrated up to an 8-fold enhanced analytical sensitivity and quantification among LFAs for influenza, malaria, and Clostridium difficile. Systematic characterization of the laser, infrared camera, and other components of the reader and their integration into a working reader instrument are described. The development of the TCA reader enables simple, highly sensitive quantification of LFAs at the point-of-care.\n
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\n \n\n \n \n \n \n \n \n Nanoscience and Nanotechnology Impacting Diverse Fields of Science, Engineering, and Medicine.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n ACS Nano, 10(12): 10615–10617. December 2016.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"NanosciencePaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{noauthor_nanoscience_2016,\n\ttitle = {Nanoscience and {Nanotechnology} {Impacting} {Diverse} {Fields} of {Science}, {Engineering}, and {Medicine}},\n\tvolume = {10},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.6b08335},\n\tdoi = {10.1021/acsnano.6b08335},\n\tnumber = {12},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tmonth = dec,\n\tyear = {2016},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {10615--10617},\n\tfile = {Full Text PDF:files/1938/2016 - Nanoscience and Nanotechnology Impacting Diverse F.pdf:application/pdf;ACS Full Text Snapshot:files/1939/acsnano.html:text/html},\n}\n\n
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\n \n\n \n \n \n \n \n \n Controlling DNA–nanoparticle serum interactions.\n \n \n \n \n\n\n \n Zagorovsky, K., Chou, L. Y. T., & Chan, W. C. W.\n\n\n \n\n\n\n PNAS, 113(48): 13600–13605. November 2016.\n Publisher: National Academy of Sciences Section: Physical Sciences\n\n\n\n
\n\n\n\n \n \n \"ControllingPaper\n  \n \n \n \"Controlling paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{zagorovsky_controlling_2016,\n\ttitle = {Controlling {DNA}–nanoparticle serum interactions},\n\tvolume = {113},\n\tcopyright = {©  . http://www.pnas.org.myaccess.library.utoronto.ca/site/misc/userlicense.xhtml},\n\tissn = {0027-8424, 1091-6490},\n\turl = {http://www.pnas.org/content/113/48/13600},\n\tdoi = {10.1073/pnas.1610028113},\n\tabstract = {Understanding the interaction of molecularly assembled nanoparticles with physiological fluids is critical to their use for in vivo delivery of drugs and contrast agents. Here, we systematically investigated the factors and mechanisms that govern the degradation of DNA on the nanoparticle surface in serum. We discovered that a higher DNA density, shorter oligonucleotides, and thicker PEG layer increased protection of DNA against serum degradation. Oligonucleotides on the surface of nanoparticles were highly resistant to DNase I endonucleases, and degradation was carried out exclusively by protein-mediated exonuclease cleavage and full-strand desorption. These results enabled the programming of the degradation rates of the DNA-assembled nanoparticle system from 0.1 to 0.7 h−1 and the engineering of superstructures that can release two different preloaded dye molecules with distinct kinetics and half-lives ranging from 3.3 to 9.8 h. This study provides a general framework for investigating the serum stability of DNA-containing nanostructures. The results advance our understanding of engineering principles for designing nanoparticle assemblies with controlled in vivo behavior and present a strategy for storage and multistage release of drugs and contrast agents that can facilitate the diagnosis and treatment of cancer and other diseases.},\n\tlanguage = {en},\n\tnumber = {48},\n\turldate = {2021-11-06},\n\tjournal = {PNAS},\n\tauthor = {Zagorovsky, Kyryl and Chou, Leo Y. T. and Chan, Warren C. W.},\n\tmonth = nov,\n\tyear = {2016},\n\tpmid = {27856755},\n\tnote = {Publisher: National Academy of Sciences\nSection: Physical Sciences},\n\tkeywords = {controlled cargo release, DNA nanostructures, nanoparticle assembly, serum resistance, serum stability},\n\tpages = {13600--13605},\n\tfile = {Full Text PDF:files/1942/Zagorovsky et al. - 2016 - Controlling DNA–nanoparticle serum interactions.pdf:application/pdf;Snapshot:files/1943/13600.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/13600.full_.pdf}\n}\n\n
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\n Understanding the interaction of molecularly assembled nanoparticles with physiological fluids is critical to their use for in vivo delivery of drugs and contrast agents. Here, we systematically investigated the factors and mechanisms that govern the degradation of DNA on the nanoparticle surface in serum. We discovered that a higher DNA density, shorter oligonucleotides, and thicker PEG layer increased protection of DNA against serum degradation. Oligonucleotides on the surface of nanoparticles were highly resistant to DNase I endonucleases, and degradation was carried out exclusively by protein-mediated exonuclease cleavage and full-strand desorption. These results enabled the programming of the degradation rates of the DNA-assembled nanoparticle system from 0.1 to 0.7 h−1 and the engineering of superstructures that can release two different preloaded dye molecules with distinct kinetics and half-lives ranging from 3.3 to 9.8 h. This study provides a general framework for investigating the serum stability of DNA-containing nanostructures. The results advance our understanding of engineering principles for designing nanoparticle assemblies with controlled in vivo behavior and present a strategy for storage and multistage release of drugs and contrast agents that can facilitate the diagnosis and treatment of cancer and other diseases.\n
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\n \n\n \n \n \n \n \n \n Mechanism of hard-nanomaterial clearance by the liver.\n \n \n \n \n\n\n \n Tsoi, K. M., MacParland, S. A., Ma, X., Spetzler, V. N., Echeverri, J., Ouyang, B., Fadel, S. M., Sykes, E. A., Goldaracena, N., Kaths, J. M., Conneely, J. B., Alman, B. A., Selzner, M., Ostrowski, M. A., Adeyi, O. A., Zilman, A., McGilvray, I. D., & Chan, W. C. W.\n\n\n \n\n\n\n Nature Mater, 15(11): 1212–1221. November 2016.\n Bandiera_abtest: a Cg_type: Nature Research Journals Number: 11 Primary_atype: Research Publisher: Nature Publishing Group Subject_term: Drug delivery;Nanoparticles Subject_term_id: drug-delivery;nanoparticles\n\n\n\n
\n\n\n\n \n \n \"MechanismPaper\n  \n \n \n \"Mechanism paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n\n\n\n
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@article{tsoi_mechanism_2016,\n\ttitle = {Mechanism of hard-nanomaterial clearance by the liver},\n\tvolume = {15},\n\tcopyright = {2016 Nature Publishing Group},\n\tissn = {1476-4660},\n\turl = {https://www.nature.com/articles/nmat4718},\n\tdoi = {10.1038/nmat4718},\n\tabstract = {The liver and spleen are major biological barriers to translating nanomedicines because they sequester the majority of administered nanomaterials and prevent delivery to diseased tissue. Here we examined the blood clearance mechanism of administered hard nanomaterials in relation to blood flow dynamics, organ microarchitecture and cellular phenotype. We found that nanomaterial velocity reduces 1,000-fold as they enter and traverse the liver, leading to 7.5 times more nanomaterial interaction with hepatic cells relative to peripheral cells. In the liver, Kupffer cells (84.8 ± 6.4\\%), hepatic B cells (81.5 ± 9.3\\%) and liver sinusoidal endothelial cells (64.6 ± 13.7\\%) interacted with administered PEGylated quantum dots, but splenic macrophages took up less material (25.4 ± 10.1\\%) due to differences in phenotype. The uptake patterns were similar for two other nanomaterial types and five different surface chemistries. Potential new strategies to overcome off-target nanomaterial accumulation may involve manipulating intra-organ flow dynamics and modulating the cellular phenotype to alter hepatic cell interactions.},\n\tlanguage = {en},\n\tnumber = {11},\n\turldate = {2021-11-06},\n\tjournal = {Nature Mater},\n\tauthor = {Tsoi, Kim M. and MacParland, Sonya A. and Ma, Xue-Zhong and Spetzler, Vinzent N. and Echeverri, Juan and Ouyang, Ben and Fadel, Saleh M. and Sykes, Edward A. and Goldaracena, Nicolas and Kaths, Johann M. and Conneely, John B. and Alman, Benjamin A. and Selzner, Markus and Ostrowski, Mario A. and Adeyi, Oyedele A. and Zilman, Anton and McGilvray, Ian D. and Chan, Warren C. W.},\n\tmonth = nov,\n\tyear = {2016},\n\tnote = {Bandiera\\_abtest: a\nCg\\_type: Nature Research Journals\nNumber: 11\nPrimary\\_atype: Research\nPublisher: Nature Publishing Group\nSubject\\_term: Drug delivery;Nanoparticles\nSubject\\_term\\_id: drug-delivery;nanoparticles},\n\tkeywords = {Drug delivery, Nanoparticles},\n\tpages = {1212--1221},\n\tfile = {Full Text PDF:files/1946/Tsoi et al. - 2016 - Mechanism of hard-nanomaterial clearance by the li.pdf:application/pdf;Snapshot:files/1948/nmat4718.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nmat4718-min.pdf}\n}\n\n
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\n The liver and spleen are major biological barriers to translating nanomedicines because they sequester the majority of administered nanomaterials and prevent delivery to diseased tissue. Here we examined the blood clearance mechanism of administered hard nanomaterials in relation to blood flow dynamics, organ microarchitecture and cellular phenotype. We found that nanomaterial velocity reduces 1,000-fold as they enter and traverse the liver, leading to 7.5 times more nanomaterial interaction with hepatic cells relative to peripheral cells. In the liver, Kupffer cells (84.8 ± 6.4%), hepatic B cells (81.5 ± 9.3%) and liver sinusoidal endothelial cells (64.6 ± 13.7%) interacted with administered PEGylated quantum dots, but splenic macrophages took up less material (25.4 ± 10.1%) due to differences in phenotype. The uptake patterns were similar for two other nanomaterial types and five different surface chemistries. Potential new strategies to overcome off-target nanomaterial accumulation may involve manipulating intra-organ flow dynamics and modulating the cellular phenotype to alter hepatic cell interactions.\n
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\n \n\n \n \n \n \n \n \n Nanoparticle–liver interactions: Cellular uptake and hepatobiliary elimination.\n \n \n \n \n\n\n \n Zhang, Y., Poon, W., Tavares, A. J., McGilvray, I. D., & Chan, W. C. W.\n\n\n \n\n\n\n Journal of Controlled Release, 240: 332–348. October 2016.\n \n\n\n\n
\n\n\n\n \n \n \"Nanoparticle–liverPaper\n  \n \n \n \"Nanoparticle–liver paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{zhang_nanoparticleliver_2016,\n\tseries = {{SI}: {North} {America} {Part} {II}},\n\ttitle = {Nanoparticle–liver interactions: {Cellular} uptake and hepatobiliary elimination},\n\tvolume = {240},\n\tissn = {0168-3659},\n\tshorttitle = {Nanoparticle–liver interactions},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0168365916300190},\n\tdoi = {10.1016/j.jconrel.2016.01.020},\n\tabstract = {30–99\\% of administered nanoparticles will accumulate and sequester in the liver after administration into the body. This results in reduced delivery to the targeted diseased tissue and potentially leads to increased toxicity at the hepatic cellular level. This review article focuses on the inter- and intra-cellular interaction between nanoparticles and hepatic cells, the elimination mechanism of nanoparticles through the hepatobiliary system, and current strategies to manipulate liver sequestration. The ability to solve the “nanoparticle-liver” interaction is critical to the clinical translation of nanotechnology for diagnosing and treating cancer, diabetes, cardiovascular disorders, and other diseases.},\n\tlanguage = {en},\n\turldate = {2021-11-06},\n\tjournal = {Journal of Controlled Release},\n\tauthor = {Zhang, Yi-Nan and Poon, Wilson and Tavares, Anthony J. and McGilvray, Ian D. and Chan, Warren C. W.},\n\tmonth = oct,\n\tyear = {2016},\n\tkeywords = {Hepatobiliary clearance, Liver, Macrophage, Nanoparticle},\n\tpages = {332--348},\n\tfile = {ScienceDirect Full Text PDF:files/1947/Zhang et al. - 2016 - Nanoparticle–liver interactions Cellular uptake a.pdf:application/pdf},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/1-s2.0-S0168365916300190-main-min.pdf}\n}\n\n
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\n 30–99% of administered nanoparticles will accumulate and sequester in the liver after administration into the body. This results in reduced delivery to the targeted diseased tissue and potentially leads to increased toxicity at the hepatic cellular level. This review article focuses on the inter- and intra-cellular interaction between nanoparticles and hepatic cells, the elimination mechanism of nanoparticles through the hepatobiliary system, and current strategies to manipulate liver sequestration. The ability to solve the “nanoparticle-liver” interaction is critical to the clinical translation of nanotechnology for diagnosing and treating cancer, diabetes, cardiovascular disorders, and other diseases.\n
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\n \n\n \n \n \n \n \n \n Tuning the Drug Loading and Release of DNA-Assembled Gold-Nanorod Superstructures.\n \n \n \n \n\n\n \n Raeesi, V., Chou, L. Y. T., & Chan, W. C. W.\n\n\n \n\n\n\n Advanced Materials, 28(38): 8511–8518. 2016.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.201600773\n\n\n\n
\n\n\n\n \n \n \"TuningPaper\n  \n \n \n \"Tuning paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{raeesi_tuning_2016,\n\ttitle = {Tuning the {Drug} {Loading} and {Release} of {DNA}-{Assembled} {Gold}-{Nanorod} {Superstructures}},\n\tvolume = {28},\n\tissn = {1521-4095},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/adma.201600773},\n\tdoi = {10.1002/adma.201600773},\n\tabstract = {The use of DNA to assemble inorganic nanoparticles into superstructures is an emerging strategy to build non-toxic delivery vehicles for targeting diseases in the body. The impact of the core–satellite nanosystem design in mediating drug storage, drug release (via heat), and killing of HeLa cells in culture is investigated.},\n\tnumber = {38},\n\turldate = {2021-11-06},\n\tjournal = {Advanced Materials},\n\tauthor = {Raeesi, Vahid and Chou, Leo Y. T. and Chan, Warren C. W.},\n\tyear = {2016},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.201600773},\n\tkeywords = {cancer, controlled drug release, core–satellite, DNA assembly, gold nanorods, nanomedicine, nanotechnology},\n\tpages = {8511--8518},\n\tfile = {Full Text PDF:files/1950/Raeesi et al. - 2016 - Tuning the Drug Loading and Release of DNA-Assembl.pdf:application/pdf;Snapshot:files/1952/adma.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/adma.201600773.pdf}\n}\n\n
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\n The use of DNA to assemble inorganic nanoparticles into superstructures is an emerging strategy to build non-toxic delivery vehicles for targeting diseases in the body. The impact of the core–satellite nanosystem design in mediating drug storage, drug release (via heat), and killing of HeLa cells in culture is investigated.\n
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\n \n\n \n \n \n \n \n \n Patients, Here Comes More Nanotechnology.\n \n \n \n \n\n\n \n Chan, W. C. W., Udugama, B., Kadhiresan, P., Kim, J., Mubareka, S., Weiss, P. S., & Parak, W. J.\n\n\n \n\n\n\n ACS Nano, 10(9): 8139–8142. September 2016.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"Patients,Paper\n  \n \n \n \"Patients, paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{chan_patients_2016,\n\ttitle = {Patients, {Here} {Comes} {More} {Nanotechnology}},\n\tvolume = {10},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.6b05610},\n\tdoi = {10.1021/acsnano.6b05610},\n\tabstract = {We describe the current difference in reporting the performance of nanotechnology diagnostic devices between technologists and clinicians. This perspective specifies the “metrics” used to evaluate these devices and describes strategies to bridge the gap between these two communities in order to accelerate the translation from academic bench to the clinic. We use two recently published ACS Nano articles to highlight the evaluation of silicon nanowire and surface-enhanced Raman spectroscopy-breath diagnostic tests for patients afflicted with cancer and asthma. These studies represent some of the earliest studies of emerging nanotechnology devices utilizing clinical parameters to assess performance.},\n\tnumber = {9},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Chan, Warren C. W. and Udugama, Buddhisha and Kadhiresan, Pranav and Kim, Jisung and Mubareka, Samira and Weiss, Paul S. and Parak, Wolfgang J.},\n\tmonth = sep,\n\tyear = {2016},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {8139--8142},\n\tfile = {Full Text PDF:files/1953/Chan et al. - 2016 - Patients, Here Comes More Nanotechnology.pdf:application/pdf;ACS Full Text Snapshot:files/1958/acsnano.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acsnano.6b05610.pdf}\n}\n\n
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\n We describe the current difference in reporting the performance of nanotechnology diagnostic devices between technologists and clinicians. This perspective specifies the “metrics” used to evaluate these devices and describes strategies to bridge the gap between these two communities in order to accelerate the translation from academic bench to the clinic. We use two recently published ACS Nano articles to highlight the evaluation of silicon nanowire and surface-enhanced Raman spectroscopy-breath diagnostic tests for patients afflicted with cancer and asthma. These studies represent some of the earliest studies of emerging nanotechnology devices utilizing clinical parameters to assess performance.\n
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\n \n\n \n \n \n \n \n \n Reply to “Evaluation of nanomedicines: stick to the basics”.\n \n \n \n \n\n\n \n Wilhelm, S., Tavares, A. J., & Chan, W. C. W.\n\n\n \n\n\n\n Nat Rev Mater, 1(10): 1–2. September 2016.\n Bandiera_abtest: a Cg_type: Nature Research Journals Number: 10 Primary_atype: Correspondence Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n \"ReplyPaper\n  \n \n \n \"Reply paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{wilhelm_reply_2016,\n\ttitle = {Reply to “{Evaluation} of nanomedicines: stick to the basics”},\n\tvolume = {1},\n\tcopyright = {2016 Macmillan Publishers Limited},\n\tissn = {2058-8437},\n\tshorttitle = {Reply to “{Evaluation} of nanomedicines},\n\turl = {https://www.nature.com/articles/natrevmats201674},\n\tdoi = {10.1038/natrevmats.2016.74},\n\tlanguage = {en},\n\tnumber = {10},\n\turldate = {2021-11-06},\n\tjournal = {Nat Rev Mater},\n\tauthor = {Wilhelm, Stefan and Tavares, Anthony J. and Chan, Warren C. W.},\n\tmonth = sep,\n\tyear = {2016},\n\tnote = {Bandiera\\_abtest: a\nCg\\_type: Nature Research Journals\nNumber: 10\nPrimary\\_atype: Correspondence\nPublisher: Nature Publishing Group},\n\tkeywords = {Biomaterials, Condensed Matter Physics, general, Materials Science, Nanotechnology, Optical and Electronic Materials},\n\tpages = {1--2},\n\tfile = {Full Text PDF:files/1955/Wilhelm et al. - 2016 - Reply to “Evaluation of nanomedicines stick to th.pdf:application/pdf;Snapshot:files/1956/natrevmats201674.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2022/01/Wilhelm-et-al.-2016-Reply-to-Evaluation-of-nanomedicines-stick-to-th.pdf}\n}\n\n
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\n \n\n \n \n \n \n \n \n A versatile plasmonic thermogel for disinfection of antimicrobial resistant bacteria.\n \n \n \n \n\n\n \n Abdou Mohamed, M. A., Raeesi, V., Turner, P. V., Rebbapragada, A., Banks, K., & Chan, W. C. W.\n\n\n \n\n\n\n Biomaterials, 97: 154–163. August 2016.\n \n\n\n\n
\n\n\n\n \n \n \"APaper\n  \n \n \n \"A paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{abdou_mohamed_versatile_2016,\n\ttitle = {A versatile plasmonic thermogel for disinfection of antimicrobial resistant bacteria},\n\tvolume = {97},\n\tissn = {0142-9612},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0142961216301144},\n\tdoi = {10.1016/j.biomaterials.2016.04.009},\n\tabstract = {The increasing occurrence of antimicrobial resistance among bacteria is a global problem that requires the development of alternative techniques to eradicate these superbugs. Herein, we used a combination of thermosensitive biocompatible polymer and gold nanorods to specifically deliver, preserve and confine heat to the area of interest. Our data demonstrates that this technique can be used to kill both Gram positive and Gram negative antimicrobial resistant bacteria in vitro. Our approach significantly reduces the antimicrobial resistant bacteria load in experimentally infected wounds by 98\\% without harming the surrounding tissues. More importantly, this polymer-nanocomposite can be prepared easily and applied to the wounds, can generate heat using a hand-held laser device, is safe for the operator, and does not have any adverse effects on the wound tissue and healing process.},\n\tlanguage = {en},\n\turldate = {2021-11-06},\n\tjournal = {Biomaterials},\n\tauthor = {Abdou Mohamed, Mohamed A. and Raeesi, Vahid and Turner, Patricia V. and Rebbapragada, Anu and Banks, Kate and Chan, Warren C. W.},\n\tmonth = aug,\n\tyear = {2016},\n\tkeywords = {Antibiotic resistant bacteria, Gold nanorods, Photothermal, Thermogel, Wound infections},\n\tpages = {154--163},\n\tfile = {ScienceDirect Full Text PDF:files/1959/Abdou Mohamed et al. - 2016 - A versatile plasmonic thermogel for disinfection o.pdf:application/pdf},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/1-s2.0-S0142961216301144-main-min.pdf}\n}\n\n
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\n The increasing occurrence of antimicrobial resistance among bacteria is a global problem that requires the development of alternative techniques to eradicate these superbugs. Herein, we used a combination of thermosensitive biocompatible polymer and gold nanorods to specifically deliver, preserve and confine heat to the area of interest. Our data demonstrates that this technique can be used to kill both Gram positive and Gram negative antimicrobial resistant bacteria in vitro. Our approach significantly reduces the antimicrobial resistant bacteria load in experimentally infected wounds by 98% without harming the surrounding tissues. More importantly, this polymer-nanocomposite can be prepared easily and applied to the wounds, can generate heat using a hand-held laser device, is safe for the operator, and does not have any adverse effects on the wound tissue and healing process.\n
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\n \n\n \n \n \n \n \n \n Quantitative Comparison of Photothermal Heat Generation between Gold Nanospheres and Nanorods.\n \n \n \n \n\n\n \n Qin, Z., Wang, Y., Randrianalisoa, J., Raeesi, V., Chan, W. C. W., Lipiński, W., & Bischof, J. C.\n\n\n \n\n\n\n Sci Rep, 6(1): 29836. July 2016.\n Bandiera_abtest: a Cc_license_type: cc_by Cg_type: Nature Research Journals Number: 1 Primary_atype: Research Publisher: Nature Publishing Group Subject_term: Mechanical engineering;Nanoscience and technology Subject_term_id: mechanical-engineering;nanoscience-and-technology\n\n\n\n
\n\n\n\n \n \n \"QuantitativePaper\n  \n \n \n \"Quantitative paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n\n\n\n
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@article{qin_quantitative_2016,\n\ttitle = {Quantitative {Comparison} of {Photothermal} {Heat} {Generation} between {Gold} {Nanospheres} and {Nanorods}},\n\tvolume = {6},\n\tcopyright = {2016 The Author(s)},\n\tissn = {2045-2322},\n\turl = {https://www.nature.com/articles/srep29836},\n\tdoi = {10.1038/srep29836},\n\tabstract = {Gold nanoparticles (GNPs) are widely used for biomedical applications due to unique optical properties, established synthesis methods, and biological compatibility. Despite important applications of plasmonic heating in thermal therapy, imaging, and diagnostics, the lack of quantification in heat generation leads to difficulties in comparing the heating capability for new plasmonic nanostructures and predicting the therapeutic and diagnostic outcome. This study quantifies GNP heat generation by experimental measurements and theoretical predictions for gold nanospheres (GNS) and nanorods (GNR). Interestingly, the results show a GNP-type dependent agreement between experiment and theory. The measured heat generation of GNS matches well with theory, while the measured heat generation of GNR is only 30\\% of that predicted theoretically at peak absorption. This then leads to a surprising finding that the polydispersity, the deviation of nanoparticle size and shape from nominal value, significantly influences GNR heat generation ({\\textgreater}70\\% reduction), while having a limited effect for GNS ({\\textless}10\\% change). This work demonstrates that polydispersity is an important metric in quantitatively predicting plasmonic heat generation and provides a validated framework to quantitatively compare the heating capabilities between gold and other plasmonic nanostructures.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2021-11-06},\n\tjournal = {Sci Rep},\n\tauthor = {Qin, Zhenpeng and Wang, Yiru and Randrianalisoa, Jaona and Raeesi, Vahid and Chan, Warren C. W. and Lipiński, Wojciech and Bischof, John C.},\n\tmonth = jul,\n\tyear = {2016},\n\tnote = {Bandiera\\_abtest: a\nCc\\_license\\_type: cc\\_by\nCg\\_type: Nature Research Journals\nNumber: 1\nPrimary\\_atype: Research\nPublisher: Nature Publishing Group\nSubject\\_term: Mechanical engineering;Nanoscience and technology\nSubject\\_term\\_id: mechanical-engineering;nanoscience-and-technology},\n\tkeywords = {Mechanical engineering, Nanoscience and technology},\n\tpages = {29836},\n\tfile = {Full Text PDF:files/1962/Qin et al. - 2016 - Quantitative Comparison of Photothermal Heat Gener.pdf:application/pdf;Snapshot:files/1966/srep29836.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/srep29836-min.pdf}\n}\n\n
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\n Gold nanoparticles (GNPs) are widely used for biomedical applications due to unique optical properties, established synthesis methods, and biological compatibility. Despite important applications of plasmonic heating in thermal therapy, imaging, and diagnostics, the lack of quantification in heat generation leads to difficulties in comparing the heating capability for new plasmonic nanostructures and predicting the therapeutic and diagnostic outcome. This study quantifies GNP heat generation by experimental measurements and theoretical predictions for gold nanospheres (GNS) and nanorods (GNR). Interestingly, the results show a GNP-type dependent agreement between experiment and theory. The measured heat generation of GNS matches well with theory, while the measured heat generation of GNR is only 30% of that predicted theoretically at peak absorption. This then leads to a surprising finding that the polydispersity, the deviation of nanoparticle size and shape from nominal value, significantly influences GNR heat generation (\\textgreater70% reduction), while having a limited effect for GNS (\\textless10% change). This work demonstrates that polydispersity is an important metric in quantitatively predicting plasmonic heat generation and provides a validated framework to quantitatively compare the heating capabilities between gold and other plasmonic nanostructures.\n
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\n \n\n \n \n \n \n \n \n Three-Dimensional Optical Mapping of Nanoparticle Distribution in Intact Tissues.\n \n \n \n \n\n\n \n Sindhwani, S., Syed, A. M., Wilhelm, S., Glancy, D. R., Chen, Y. Y., Dobosz, M., & Chan, W. C. W.\n\n\n \n\n\n\n ACS Nano, 10(5): 5468–5478. May 2016.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"Three-DimensionalPaper\n  \n \n \n \"Three-Dimensional paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{sindhwani_three-dimensional_2016,\n\ttitle = {Three-{Dimensional} {Optical} {Mapping} of {Nanoparticle} {Distribution} in {Intact} {Tissues}},\n\tvolume = {10},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.6b01879},\n\tdoi = {10.1021/acsnano.6b01879},\n\tabstract = {The role of tissue architecture in mediating nanoparticle transport, targeting, and biological effects is unknown due to the lack of tools for imaging nanomaterials in whole organs. Here, we developed a rapid optical mapping technique to image nanomaterials in intact organs ex vivo and in three-dimensions (3D). We engineered a high-throughput electrophoretic flow device to simultaneously transform up to 48 tissues into optically transparent structures, allowing subcellular imaging of nanomaterials more than 1 mm deep into tissues which is 25-fold greater than current techniques. A key finding is that nanomaterials can be retained in the processed tissue by chemical cross-linking of surface adsorbed serum proteins to the tissue matrix, which enables nanomaterials to be imaged with respect to cells, blood vessels, and other structures. We developed a computational algorithm to analyze and quantitatively map nanomaterial distribution. This method can be universally applied to visualize the distribution and interactions of materials in whole tissues and animals including such applications as the imaging of nanomaterials, tissue engineered constructs, and biosensors within their intact biological environment.},\n\tnumber = {5},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Sindhwani, Shrey and Syed, Abdullah Muhammad and Wilhelm, Stefan and Glancy, Dylan R. and Chen, Yih Yang and Dobosz, Michael and Chan, Warren C. W.},\n\tmonth = may,\n\tyear = {2016},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {5468--5478},\n\tfile = {Full Text PDF:files/1963/Sindhwani et al. - 2016 - Three-Dimensional Optical Mapping of Nanoparticle .pdf:application/pdf;ACS Full Text Snapshot:files/1971/acsnano.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acsnano.6b01879-min.pdf}\n}\n\n
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\n The role of tissue architecture in mediating nanoparticle transport, targeting, and biological effects is unknown due to the lack of tools for imaging nanomaterials in whole organs. Here, we developed a rapid optical mapping technique to image nanomaterials in intact organs ex vivo and in three-dimensions (3D). We engineered a high-throughput electrophoretic flow device to simultaneously transform up to 48 tissues into optically transparent structures, allowing subcellular imaging of nanomaterials more than 1 mm deep into tissues which is 25-fold greater than current techniques. A key finding is that nanomaterials can be retained in the processed tissue by chemical cross-linking of surface adsorbed serum proteins to the tissue matrix, which enables nanomaterials to be imaged with respect to cells, blood vessels, and other structures. We developed a computational algorithm to analyze and quantitatively map nanomaterial distribution. This method can be universally applied to visualize the distribution and interactions of materials in whole tissues and animals including such applications as the imaging of nanomaterials, tissue engineered constructs, and biosensors within their intact biological environment.\n
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\n \n\n \n \n \n \n \n \n Clinical Validation of Quantum Dot Barcode Diagnostic Technology.\n \n \n \n \n\n\n \n Kim, J., Biondi, M. J., Feld, J. J., & Chan, W. C. W.\n\n\n \n\n\n\n ACS Nano, 10(4): 4742–4753. April 2016.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"ClinicalPaper\n  \n \n \n \"Clinical paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{kim_clinical_2016,\n\ttitle = {Clinical {Validation} of {Quantum} {Dot} {Barcode} {Diagnostic} {Technology}},\n\tvolume = {10},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.6b01254},\n\tdoi = {10.1021/acsnano.6b01254},\n\tabstract = {There has been a major focus on the clinical translation of emerging technologies for diagnosing patients with infectious diseases, cancer, heart disease, and diabetes. However, most developments still remain at the academic stage where researchers use spiked target molecules to demonstrate the utility of a technology and assess the analytical performance. This approach does not account for the biological complexities and variabilities of human patient samples. As a technology matures and potentially becomes clinically viable, one important intermediate step in the translation process is to conduct a full clinical validation of the technology using a large number of patient samples. Here, we present a full detailed clinical validation of Quantum Dot (QD) barcode technology for diagnosing patients infected with Hepatitis B Virus (HBV). We further demonstrate that the detection of multiple regions of the viral genome using multiplexed QD barcodes improved clinical sensitivity from 54.9–66.7\\% to 80.4–90.5\\%, and describe how to use QD barcodes for optimal clinical diagnosis of patients. The use of QDs in biology and medicine was first introduced in 1998 but has not reached clinical care. This study describes our long-term systematic development strategy to advance QD technology to a clinically feasible product for diagnosing patients. Our “blueprint” for translating the QD barcode research concept could be adapted for other nanotechnologies, to efficiently advance diagnostic techniques discovered in the academic laboratory to patient care.},\n\tnumber = {4},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Kim, Jisung and Biondi, Mia J. and Feld, Jordan J. and Chan, Warren C. W.},\n\tmonth = apr,\n\tyear = {2016},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {4742--4753},\n\tfile = {Full Text PDF:files/1968/Kim et al. - 2016 - Clinical Validation of Quantum Dot Barcode Diagnos.pdf:application/pdf;ACS Full Text Snapshot:files/1972/acsnano.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acsnano.6b01254-min.pdf}\n}\n\n
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\n There has been a major focus on the clinical translation of emerging technologies for diagnosing patients with infectious diseases, cancer, heart disease, and diabetes. However, most developments still remain at the academic stage where researchers use spiked target molecules to demonstrate the utility of a technology and assess the analytical performance. This approach does not account for the biological complexities and variabilities of human patient samples. As a technology matures and potentially becomes clinically viable, one important intermediate step in the translation process is to conduct a full clinical validation of the technology using a large number of patient samples. Here, we present a full detailed clinical validation of Quantum Dot (QD) barcode technology for diagnosing patients infected with Hepatitis B Virus (HBV). We further demonstrate that the detection of multiple regions of the viral genome using multiplexed QD barcodes improved clinical sensitivity from 54.9–66.7% to 80.4–90.5%, and describe how to use QD barcodes for optimal clinical diagnosis of patients. The use of QDs in biology and medicine was first introduced in 1998 but has not reached clinical care. This study describes our long-term systematic development strategy to advance QD technology to a clinically feasible product for diagnosing patients. Our “blueprint” for translating the QD barcode research concept could be adapted for other nanotechnologies, to efficiently advance diagnostic techniques discovered in the academic laboratory to patient care.\n
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\n \n\n \n \n \n \n \n \n Analysis of nanoparticle delivery to tumours.\n \n \n \n \n\n\n \n Wilhelm, S., Tavares, A. J., Dai, Q., Ohta, S., Audet, J., Dvorak, H. F., & Chan, W. C. W.\n\n\n \n\n\n\n Nat Rev Mater, 1(5): 1–12. April 2016.\n Bandiera_abtest: a Cg_type: Nature Research Journals Number: 5 Primary_atype: Reviews Publisher: Nature Publishing Group Subject_term: Cancer therapy;Medical research;Nanoparticles Subject_term_id: cancer-therapy;medical-research;nanoparticles\n\n\n\n
\n\n\n\n \n \n \"AnalysisPaper\n  \n \n \n \"Analysis paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n\n\n\n
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@article{wilhelm_analysis_2016,\n\ttitle = {Analysis of nanoparticle delivery to tumours},\n\tvolume = {1},\n\tcopyright = {2016 Macmillan Publishers Limited},\n\tissn = {2058-8437},\n\turl = {https://www.nature.com/articles/natrevmats201614},\n\tdoi = {10.1038/natrevmats.2016.14},\n\tabstract = {Targeting nanoparticles to malignant tissues for improved diagnosis and therapy is a popular concept. However, after surveying the literature from the past 10 years, only 0.7\\% (median) of the administered nanoparticle dose is found to be delivered to a solid tumour. This has negative consequences on the translation of nanotechnology for human use with respect to manufacturing, cost, toxicity, and imaging and therapeutic efficacy. In this article, we conduct a multivariate analysis on the compiled data to reveal the contributions of nanoparticle physicochemical parameters, tumour models and cancer types on the low delivery efficiency. We explore the potential causes of the poor delivery efficiency from the perspectives of tumour biology (intercellular versus transcellular transport, enhanced permeability and retention effect, and physicochemical-dependent nanoparticle transport through the tumour stroma) as well as competing organs (mononuclear phagocytic and renal systems) and present a 30-year research strategy to overcome this fundamental limitation. Solving the nanoparticle delivery problem will accelerate the clinical translation of nanomedicine.},\n\tlanguage = {en},\n\tnumber = {5},\n\turldate = {2021-11-06},\n\tjournal = {Nat Rev Mater},\n\tauthor = {Wilhelm, Stefan and Tavares, Anthony J. and Dai, Qin and Ohta, Seiichi and Audet, Julie and Dvorak, Harold F. and Chan, Warren C. W.},\n\tmonth = apr,\n\tyear = {2016},\n\tnote = {Bandiera\\_abtest: a\nCg\\_type: Nature Research Journals\nNumber: 5\nPrimary\\_atype: Reviews\nPublisher: Nature Publishing Group\nSubject\\_term: Cancer therapy;Medical research;Nanoparticles\nSubject\\_term\\_id: cancer-therapy;medical-research;nanoparticles},\n\tkeywords = {Cancer therapy, Medical research, Nanoparticles},\n\tpages = {1--12},\n\tfile = {Snapshot:files/1970/natrevmats201614.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/natrevmats201614.pdf}\n}\n\n
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\n Targeting nanoparticles to malignant tissues for improved diagnosis and therapy is a popular concept. However, after surveying the literature from the past 10 years, only 0.7% (median) of the administered nanoparticle dose is found to be delivered to a solid tumour. This has negative consequences on the translation of nanotechnology for human use with respect to manufacturing, cost, toxicity, and imaging and therapeutic efficacy. In this article, we conduct a multivariate analysis on the compiled data to reveal the contributions of nanoparticle physicochemical parameters, tumour models and cancer types on the low delivery efficiency. We explore the potential causes of the poor delivery efficiency from the perspectives of tumour biology (intercellular versus transcellular transport, enhanced permeability and retention effect, and physicochemical-dependent nanoparticle transport through the tumour stroma) as well as competing organs (mononuclear phagocytic and renal systems) and present a 30-year research strategy to overcome this fundamental limitation. Solving the nanoparticle delivery problem will accelerate the clinical translation of nanomedicine.\n
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\n \n\n \n \n \n \n \n \n Engineering the Structure and Properties of DNA-Nanoparticle Superstructures Using Polyvalent Counterions.\n \n \n \n \n\n\n \n Chou, L. Y. T., Song, F., & Chan, W. C. W.\n\n\n \n\n\n\n J. Am. Chem. Soc., 138(13): 4565–4572. April 2016.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"EngineeringPaper\n  \n \n \n \"Engineering paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 4 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{chou_engineering_2016,\n\ttitle = {Engineering the {Structure} and {Properties} of {DNA}-{Nanoparticle} {Superstructures} {Using} {Polyvalent} {Counterions}},\n\tvolume = {138},\n\tissn = {0002-7863},\n\turl = {https://doi.org/10.1021/jacs.6b00751},\n\tdoi = {10.1021/jacs.6b00751},\n\tabstract = {DNA assembly of nanoparticles is a powerful approach to control their properties and prototype new materials. However, the structure and properties of DNA-assembled nanoparticles are labile and sensitive to interactions with counterions, which vary with processing and application environment. Here we show that substituting polyamines in place of elemental counterions significantly enhanced the structural rigidity and plasmonic properties of DNA-assembled metal nanoparticles. These effects arose from the ability of polyamines to condense DNA and cross-link DNA-coated nanoparticles. We further used polyamine wrapped DNA nanostructures as structural templates to seed the growth of polymer multilayers via layer-by-layer assembly, and controlled the degree of DNA condensation, plasmon coupling efficiency, and material responsiveness to environmental stimuli by varying polyelectrolyte composition. These results highlight counterion engineering as a versatile strategy to tailor the properties of DNA-nanoparticle assemblies for various applications, and should be applicable to other classes of DNA nanostructures.},\n\tnumber = {13},\n\turldate = {2021-11-06},\n\tjournal = {J. Am. Chem. Soc.},\n\tauthor = {Chou, Leo Y. T. and Song, Fayi and Chan, Warren C. W.},\n\tmonth = apr,\n\tyear = {2016},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {4565--4572},\n\tfile = {Full Text PDF:files/1969/Chou et al. - 2016 - Engineering the Structure and Properties of DNA-Na.pdf:application/pdf;ACS Full Text Snapshot:files/1973/jacs.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/jacs.6b00751-min.pdf}\n}\n\n
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\n DNA assembly of nanoparticles is a powerful approach to control their properties and prototype new materials. However, the structure and properties of DNA-assembled nanoparticles are labile and sensitive to interactions with counterions, which vary with processing and application environment. Here we show that substituting polyamines in place of elemental counterions significantly enhanced the structural rigidity and plasmonic properties of DNA-assembled metal nanoparticles. These effects arose from the ability of polyamines to condense DNA and cross-link DNA-coated nanoparticles. We further used polyamine wrapped DNA nanostructures as structural templates to seed the growth of polymer multilayers via layer-by-layer assembly, and controlled the degree of DNA condensation, plasmon coupling efficiency, and material responsiveness to environmental stimuli by varying polyelectrolyte composition. These results highlight counterion engineering as a versatile strategy to tailor the properties of DNA-nanoparticle assemblies for various applications, and should be applicable to other classes of DNA nanostructures.\n
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\n \n\n \n \n \n \n \n \n Tailoring nanoparticle designs to target cancer based on tumor pathophysiology.\n \n \n \n \n\n\n \n Sykes, E. A., Dai, Q., Sarsons, C. D., Chen, J., Rocheleau, J. V., Hwang, D. M., Zheng, G., Cramb, D. T., Rinker, K. D., & Chan, W. C. W.\n\n\n \n\n\n\n PNAS, 113(9): E1142–E1151. March 2016.\n Publisher: National Academy of Sciences Section: PNAS Plus\n\n\n\n
\n\n\n\n \n \n \"TailoringPaper\n  \n \n \n \"Tailoring paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{sykes_tailoring_2016,\n\ttitle = {Tailoring nanoparticle designs to target cancer based on tumor pathophysiology},\n\tvolume = {113},\n\tcopyright = {©  . http://www.pnas.org.myaccess.library.utoronto.ca/preview\\_site/misc/userlicense.xhtml},\n\tissn = {0027-8424, 1091-6490},\n\turl = {http://www.pnas.org/content/113/9/E1142},\n\tdoi = {10.1073/pnas.1521265113},\n\tabstract = {Nanoparticles can provide significant improvements in the diagnosis and treatment of cancer. How nanoparticle size, shape, and surface chemistry can affect their accumulation, retention, and penetration in tumors remains heavily investigated, because such findings provide guiding principles for engineering optimal nanosystems for tumor targeting. Currently, the experimental focus has been on particle design and not the biological system. Here, we varied tumor volume to determine whether cancer pathophysiology can influence tumor accumulation and penetration of different sized nanoparticles. Monte Carlo simulations were also used to model the process of nanoparticle accumulation. We discovered that changes in pathophysiology associated with tumor volume can selectively change tumor uptake of nanoparticles of varying size. We further determine that nanoparticle retention within tumors depends on the frequency of interaction of particles with the perivascular extracellular matrix for smaller nanoparticles, whereas transport of larger nanomaterials is dominated by Brownian motion. These results reveal that nanoparticles can potentially be personalized according to a patient’s disease state to achieve optimal diagnostic and therapeutic outcomes.},\n\tlanguage = {en},\n\tnumber = {9},\n\turldate = {2021-11-06},\n\tjournal = {PNAS},\n\tauthor = {Sykes, Edward A. and Dai, Qin and Sarsons, Christopher D. and Chen, Juan and Rocheleau, Jonathan V. and Hwang, David M. and Zheng, Gang and Cramb, David T. and Rinker, Kristina D. and Chan, Warren C. W.},\n\tmonth = mar,\n\tyear = {2016},\n\tpmid = {26884153},\n\tnote = {Publisher: National Academy of Sciences\nSection: PNAS Plus},\n\tkeywords = {cancer, nano–bio interactions, nanoparticles, targeting, tumor},\n\tpages = {E1142--E1151},\n\tfile = {Full Text PDF:files/1991/Sykes et al. - 2016 - Tailoring nanoparticle designs to target cancer ba.pdf:application/pdf;Snapshot:files/1993/E1142.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/E1142.full_.pdf}\n}\n\n
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\n Nanoparticles can provide significant improvements in the diagnosis and treatment of cancer. How nanoparticle size, shape, and surface chemistry can affect their accumulation, retention, and penetration in tumors remains heavily investigated, because such findings provide guiding principles for engineering optimal nanosystems for tumor targeting. Currently, the experimental focus has been on particle design and not the biological system. Here, we varied tumor volume to determine whether cancer pathophysiology can influence tumor accumulation and penetration of different sized nanoparticles. Monte Carlo simulations were also used to model the process of nanoparticle accumulation. We discovered that changes in pathophysiology associated with tumor volume can selectively change tumor uptake of nanoparticles of varying size. We further determine that nanoparticle retention within tumors depends on the frequency of interaction of particles with the perivascular extracellular matrix for smaller nanoparticles, whereas transport of larger nanomaterials is dominated by Brownian motion. These results reveal that nanoparticles can potentially be personalized according to a patient’s disease state to achieve optimal diagnostic and therapeutic outcomes.\n
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\n \n\n \n \n \n \n \n \n DNA-controlled dynamic colloidal nanoparticle systems for mediating cellular interaction.\n \n \n \n \n\n\n \n Ohta, S., Glancy, D., & Chan, W. C. W.\n\n\n \n\n\n\n Science, 351(6275): 841–845. February 2016.\n Publisher: American Association for the Advancement of Science\n\n\n\n
\n\n\n\n \n \n \"DNA-controlledPaper\n  \n \n \n \"DNA-controlled paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n  \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{ohta_dna-controlled_2016,\n\ttitle = {{DNA}-controlled dynamic colloidal nanoparticle systems for mediating cellular interaction},\n\tvolume = {351},\n\turl = {https://www.science.org/doi/full/10.1126/science.aad4925},\n\tdoi = {10.1126/science.aad4925},\n\tnumber = {6275},\n\turldate = {2021-11-06},\n\tjournal = {Science},\n\tauthor = {Ohta, Seiichi and Glancy, Dylan and Chan, Warren C. W.},\n\tmonth = feb,\n\tyear = {2016},\n\tnote = {Publisher: American Association for the Advancement of Science},\n\tpages = {841--845},\n\tfile = {Full Text PDF:files/1995/Ohta et al. - 2016 - DNA-controlled dynamic colloidal nanoparticle syst.pdf:application/pdf},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/841.full_.pdf}\n}\n\n
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\n \n\n \n \n \n \n \n \n Highly efficient adenoviral transduction of pancreatic islets using a microfluidic device.\n \n \n \n \n\n\n \n N. Silva, P., Atto, Z., Regeenes, R., Tufa, U., Yang Chen, Y., W. Chan, W. C., Volchuk, A., M. Kilkenny, D., & V. Rocheleau, J.\n\n\n \n\n\n\n Lab on a Chip, 16(15): 2921–2934. 2016.\n Publisher: Royal Society of Chemistry\n\n\n\n
\n\n\n\n \n \n \"HighlyPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{nsilva_highly_2016,\n\ttitle = {Highly efficient adenoviral transduction of pancreatic islets using a microfluidic device},\n\tvolume = {16},\n\turl = {http://pubs.rsc.org/en/content/articlelanding/2016/lc/c6lc00345a},\n\tdoi = {10.1039/C6LC00345A},\n\tlanguage = {en},\n\tnumber = {15},\n\turldate = {2021-11-06},\n\tjournal = {Lab on a Chip},\n\tauthor = {N. Silva, Pamuditha and Atto, Zaid and Regeenes, Romario and Tufa, Uilki and Yang Chen, Yih and W. Chan, Warren C. and Volchuk, Allen and M. Kilkenny, Dawn and V. Rocheleau, Jonathan},\n\tyear = {2016},\n\tnote = {Publisher: Royal Society of Chemistry},\n\tpages = {2921--2934},\n\tfile = {Snapshot:files/1998/c6lc00345a.html:text/html;Full Text PDF:files/2003/N. Silva et al. - 2016 - Highly efficient adenoviral transduction of pancre.pdf:application/pdf},\n}\n\n
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\n \n\n \n \n \n \n \n \n Improving nanoparticle diffusion through tumor collagen matrix by photo-thermal gold nanorods.\n \n \n \n \n\n\n \n Raeesi, V., & W. Chan, W. C.\n\n\n \n\n\n\n Nanoscale, 8(25): 12524–12530. 2016.\n Publisher: Royal Society of Chemistry\n\n\n\n
\n\n\n\n \n \n \"ImprovingPaper\n  \n \n \n \"Improving paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{raeesi_improving_2016,\n\ttitle = {Improving nanoparticle diffusion through tumor collagen matrix by photo-thermal gold nanorods},\n\tvolume = {8},\n\turl = {http://pubs.rsc.org/en/content/articlelanding/2016/nr/c5nr08463f},\n\tdoi = {10.1039/C5NR08463F},\n\tlanguage = {en},\n\tnumber = {25},\n\turldate = {2021-11-06},\n\tjournal = {Nanoscale},\n\tauthor = {Raeesi, Vahid and W. Chan, Warren C.},\n\tyear = {2016},\n\tnote = {Publisher: Royal Society of Chemistry},\n\tpages = {12524--12530},\n\tfile = {Full Text PDF:files/2001/Raeesi and W. Chan - 2016 - Improving nanoparticle diffusion through tumor col.pdf:application/pdf;Snapshot:files/2002/c5nr08463f.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/c5nr08463f-min.pdf}\n}\n\n
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\n  \n 2015\n \n \n (7)\n \n \n
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\n \n\n \n \n \n \n \n \n Prediction of nanoparticles-cell association based on corona proteins and physicochemical properties.\n \n \n \n \n\n\n \n Liu, R., Jiang, W., D. Walkey, C., W. Chan, W. C., & Cohen, Y.\n\n\n \n\n\n\n Nanoscale, 7(21): 9664–9675. 2015.\n Publisher: Royal Society of Chemistry\n\n\n\n
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@article{liu_prediction_2015,\n\ttitle = {Prediction of nanoparticles-cell association based on corona proteins and physicochemical properties},\n\tvolume = {7},\n\turl = {http://pubs.rsc.org/en/content/articlelanding/2015/nr/c5nr01537e},\n\tdoi = {10.1039/C5NR01537E},\n\tlanguage = {en},\n\tnumber = {21},\n\turldate = {2021-11-06},\n\tjournal = {Nanoscale},\n\tauthor = {Liu, Rong and Jiang, Wen and D. Walkey, Carl and W. Chan, Warren C. and Cohen, Yoram},\n\tyear = {2015},\n\tnote = {Publisher: Royal Society of Chemistry},\n\tpages = {9664--9675},\n\tfile = {Full Text PDF:files/1976/Liu et al. - 2015 - Prediction of nanoparticles-cell association based.pdf:application/pdf;Snapshot:files/1978/c5nr01537e.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/c5nr01537e-min.pdf}\n}\n\n
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\n \n\n \n \n \n \n \n \n Nanoparticle–blood interactions: the implications on solid tumour targeting.\n \n \n \n \n\n\n \n Lazarovits, J., Yang Chen, Y., A. Sykes, E., & W. Chan, W. C.\n\n\n \n\n\n\n Chemical Communications, 51(14): 2756–2767. 2015.\n Publisher: Royal Society of Chemistry\n\n\n\n
\n\n\n\n \n \n \"Nanoparticle–bloodPaper\n  \n \n \n \"Nanoparticle–blood paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{lazarovits_nanoparticleblood_2015,\n\ttitle = {Nanoparticle–blood interactions: the implications on solid tumour targeting},\n\tvolume = {51},\n\tshorttitle = {Nanoparticle–blood interactions},\n\turl = {http://pubs.rsc.org/en/content/articlelanding/2015/cc/c4cc07644c},\n\tdoi = {10.1039/C4CC07644C},\n\tlanguage = {en},\n\tnumber = {14},\n\turldate = {2021-11-06},\n\tjournal = {Chemical Communications},\n\tauthor = {Lazarovits, James and Yang Chen, Yih and A. Sykes, Edward and W. Chan, Warren C.},\n\tyear = {2015},\n\tnote = {Publisher: Royal Society of Chemistry},\n\tpages = {2756--2767},\n\tfile = {Full Text PDF:files/1977/Lazarovits et al. - 2015 - Nanoparticle–blood interactions the implications .pdf:application/pdf;Snapshot:files/1979/c4cc07644c.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/c4cc07644c-min.pdf}\n}\n\n
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\n \n\n \n \n \n \n \n \n How Nanoparticles Interact with Cancer Cells.\n \n \n \n \n\n\n \n Syed, A., & Chan, W. C. W.\n\n\n \n\n\n\n In Mirkin, C. A., Meade, T. J., Petrosko, S. H., & Stegh, A. H., editor(s), Nanotechnology-Based Precision Tools for the Detection and Treatment of Cancer, of Cancer Treatment and Research, pages 227–244. Springer International Publishing, Cham, 2015.\n \n\n\n\n
\n\n\n\n \n \n \"HowPaper\n  \n \n \n \"How paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@incollection{syed_how_2015,\n\taddress = {Cham},\n\tseries = {Cancer {Treatment} and {Research}},\n\ttitle = {How {Nanoparticles} {Interact} with {Cancer} {Cells}},\n\tisbn = {978-3-319-16555-4},\n\turl = {https://doi.org/10.1007/978-3-319-16555-4_10},\n\tabstract = {There are currently no nanoparticle formulations that optimally target diseased cells in the body. A small percentage of nanoparticles reach these cells and most accumulate in cells of the mononuclear phagocytic system. This chapter explores the interactions between nanoparticles and cells that may explain the causes for off-target accumulation of nanoparticles. A greater understanding of the nanoparticle-cellular interactions will lead to improvements in particle design for improved therapeutic outcome.},\n\tlanguage = {en},\n\turldate = {2021-11-06},\n\tbooktitle = {Nanotechnology-{Based} {Precision} {Tools} for the {Detection} and {Treatment} of {Cancer}},\n\tpublisher = {Springer International Publishing},\n\tauthor = {Syed, Abdullah and Chan, Warren C. W.},\n\teditor = {Mirkin, Chad A. and Meade, Thomas J. and Petrosko, Sarah Hurst and Stegh, Alexander H.},\n\tyear = {2015},\n\tdoi = {10.1007/978-3-319-16555-4_10},\n\tkeywords = {Cancer Targeting, Nano-Biointeractions, Nanomedicine, Nanoparticle Cell Interaction},\n\tpages = {227--244},\n\tfile = {Springer Full Text PDF:files/1981/Syed and Chan - 2015 - How Nanoparticles Interact with Cancer Cells.pdf:application/pdf},\n\turl_Paper = {https://link.springer.com/content/pdf/10.1007%2F978-3-319-16555-4.pdf}\n}\n\n
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\n There are currently no nanoparticle formulations that optimally target diseased cells in the body. A small percentage of nanoparticles reach these cells and most accumulate in cells of the mononuclear phagocytic system. This chapter explores the interactions between nanoparticles and cells that may explain the causes for off-target accumulation of nanoparticles. A greater understanding of the nanoparticle-cellular interactions will lead to improvements in particle design for improved therapeutic outcome.\n
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\n \n\n \n \n \n \n \n \n Integrated Quantum Dot Barcode Smartphone Optical Device for Wireless Multiplexed Diagnosis of Infected Patients.\n \n \n \n \n\n\n \n Ming, K., Kim, J., Biondi, M. J., Syed, A., Chen, K., Lam, A., Ostrowski, M., Rebbapragada, A., Feld, J. J., & Chan, W. C. W.\n\n\n \n\n\n\n ACS Nano, 9(3): 3060–3074. March 2015.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"IntegratedPaper\n  \n \n \n \"Integrated paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{ming_integrated_2015,\n\ttitle = {Integrated {Quantum} {Dot} {Barcode} {Smartphone} {Optical} {Device} for {Wireless} {Multiplexed} {Diagnosis} of {Infected} {Patients}},\n\tvolume = {9},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/nn5072792},\n\tdoi = {10.1021/nn5072792},\n\tabstract = {Inorganic nanoparticles are ideal precursors for engineering barcodes for rapidly detecting diseases. Despite advances in the chemical design of these barcodes, they have not advanced to clinical use because they lack sensitivity and are not cost-effective due to requirement of a large read-out system. Here we combined recent advances in quantum dot barcode technology with smartphones and isothermal amplification to engineer a simple and low-cost chip-based wireless multiplex diagnostic device. We characterized the analytical performance of this device and demonstrated that the device is capable of detecting down to 1000 viral genetic copies per milliliter, and this enabled the diagnosis of patients infected with HIV or hepatitis B. More importantly, the barcoding enabled us to detect multiple infectious pathogens simultaneously, in a single test, in less than 1 h. This multiplexing capability of the device enables the diagnosis of infections that are difficult to differentiate clinically due to common symptoms such as a fever or rash. The integration of quantum dot barcoding technology with a smartphone reader provides a capacity for global surveillance of infectious diseases and the potential to accelerate knowledge exchange transfer of emerging or exigent disease threats with healthcare and military organizations in real time.},\n\tnumber = {3},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Ming, Kevin and Kim, Jisung and Biondi, Mia J. and Syed, Abdullah and Chen, Kun and Lam, Albert and Ostrowski, Mario and Rebbapragada, Anu and Feld, Jordan J. and Chan, Warren C. W.},\n\tmonth = mar,\n\tyear = {2015},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {3060--3074},\n\tfile = {Full Text PDF:files/1984/Ming et al. - 2015 - Integrated Quantum Dot Barcode Smartphone Optical .pdf:application/pdf;ACS Full Text Snapshot:files/1987/nn5072792.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nn5072792-min.pdf}\n}\n\n
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\n Inorganic nanoparticles are ideal precursors for engineering barcodes for rapidly detecting diseases. Despite advances in the chemical design of these barcodes, they have not advanced to clinical use because they lack sensitivity and are not cost-effective due to requirement of a large read-out system. Here we combined recent advances in quantum dot barcode technology with smartphones and isothermal amplification to engineer a simple and low-cost chip-based wireless multiplex diagnostic device. We characterized the analytical performance of this device and demonstrated that the device is capable of detecting down to 1000 viral genetic copies per milliliter, and this enabled the diagnosis of patients infected with HIV or hepatitis B. More importantly, the barcoding enabled us to detect multiple infectious pathogens simultaneously, in a single test, in less than 1 h. This multiplexing capability of the device enables the diagnosis of infections that are difficult to differentiate clinically due to common symptoms such as a fever or rash. The integration of quantum dot barcoding technology with a smartphone reader provides a capacity for global surveillance of infectious diseases and the potential to accelerate knowledge exchange transfer of emerging or exigent disease threats with healthcare and military organizations in real time.\n
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\n \n\n \n \n \n \n \n \n Where Are We Heading in Nanotechnology Environmental Health and Safety and Materials Characterization?.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n ACS Nano, 9(6): 5627–5630. June 2015.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"WherePaper\n  \n \n \n \"Where paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{noauthor_where_2015,\n\ttitle = {Where {Are} {We} {Heading} in {Nanotechnology} {Environmental} {Health} and {Safety} and {Materials} {Characterization}?},\n\tvolume = {9},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.5b03496},\n\tdoi = {10.1021/acsnano.5b03496},\n\tnumber = {6},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tmonth = jun,\n\tyear = {2015},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {5627--5630},\n\tfile = {Full Text PDF:files/1985/2015 - Where Are We Heading in Nanotechnology Environment.pdf:application/pdf;ACS Full Text Snapshot:files/1986/acsnano.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acsnano.5b03496.pdf}\n}\n\n
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\n \n\n \n \n \n \n \n \n Guiding principles for a successful multidisciplinary research collaboration.\n \n \n \n \n\n\n \n Lustig, L. C, Ponzielli, R., Tang, P. S, Sathiamoorthy, S., Inamoto, I., Shin, J. A, Penn, L. Z, & Chan, W. C.\n\n\n \n\n\n\n Future Science OA, 1(3). November 2015.\n Publisher: Future Science\n\n\n\n
\n\n\n\n \n \n \"GuidingPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{lustig_guiding_2015,\n\ttitle = {Guiding principles for a successful multidisciplinary research collaboration},\n\tvolume = {1},\n\turl = {https://www.future-science.com/doi/10.4155/fso.15.1},\n\tdoi = {10.4155/fso.15.1},\n\tnumber = {3},\n\turldate = {2021-11-06},\n\tjournal = {Future Science OA},\n\tauthor = {Lustig, Lindsay C and Ponzielli, Romina and Tang, Peter S and Sathiamoorthy, Sarmitha and Inamoto, Ichiro and Shin, Jumi A and Penn, Linda Z and Chan, Warren CW},\n\tmonth = nov,\n\tyear = {2015},\n\tnote = {Publisher: Future Science},\n\tkeywords = {grant funding, guidelines, mentorship, multidisciplinary collaboration, productivity},\n\tfile = {Full Text PDF:files/1989/Lustig et al. - 2015 - Guiding principles for a successful multidisciplin.pdf:application/pdf},\n}\n\n
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\n \n\n \n \n \n \n \n \n Grand Plans for Nano.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n ACS Nano, 9(12): 11503–11505. December 2015.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"GrandPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{noauthor_grand_2015,\n\ttitle = {Grand {Plans} for {Nano}},\n\tvolume = {9},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/acsnano.5b07280},\n\tdoi = {10.1021/acsnano.5b07280},\n\tnumber = {12},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tmonth = dec,\n\tyear = {2015},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {11503--11505},\n\tfile = {Full Text PDF:files/2000/2015 - Grand Plans for Nano.pdf:application/pdf;ACS Full Text Snapshot:files/2004/acsnano.html:text/html},\n}\n\n
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\n  \n 2014\n \n \n (12)\n \n \n
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\n \n\n \n \n \n \n \n \n A Year for Nanoscience.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n ACS Nano, 8(12): 11901–11903. December 2014.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"APaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{noauthor_year_2014,\n\ttitle = {A {Year} for {Nanoscience}},\n\tvolume = {8},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/nn5070716},\n\tdoi = {10.1021/nn5070716},\n\tnumber = {12},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tmonth = dec,\n\tyear = {2014},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {11901--11903},\n\tfile = {Full Text PDF:files/2008/2014 - A Year for Nanoscience.pdf:application/pdf;ACS Full Text Snapshot:files/2010/nn5070716.html:text/html},\n}\n\n
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\n \n\n \n \n \n \n \n \n The Role of Ligand Density and Size in Mediating Quantum Dot Nuclear Transport.\n \n \n \n \n\n\n \n Tang, P. S., Sathiamoorthy, S., Lustig, L. C., Ponzielli, R., Inamoto, I., Penn, L. Z., Shin, J. A., & Chan, W. C. W.\n\n\n \n\n\n\n Small, 10(20): 4182–4192. 2014.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/smll.201401056\n\n\n\n
\n\n\n\n \n \n \"ThePaper\n  \n \n \n \"The paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{tang_role_2014,\n\ttitle = {The {Role} of {Ligand} {Density} and {Size} in {Mediating} {Quantum} {Dot} {Nuclear} {Transport}},\n\tvolume = {10},\n\tissn = {1613-6829},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/smll.201401056},\n\tdoi = {10.1002/smll.201401056},\n\tabstract = {Studying the effects of the physicochemical properties of nanomaterials on cellular uptake, toxicity, and exocytosis can provide the foundation for designing safer and more effective nanoparticles for clinical applications. However, an understanding of the effects of these properties on subcellular transport, accumulation, and distribution remains limited. The present study investigates the effects of surface density and particle size of semiconductor quantum dots on cellular uptake as well as nuclear transport kinetics, retention, and accumulation. The current work illustrates that cellular uptake and nuclear accumulation of nanoparticles depend on surface density of the nuclear localization signal (NLS) peptides with nuclear transport reaching a plateau at 20\\% surface NLS density in as little as 30 min. These intracellular nanoparticles have no effects on cell viability up to 72 h post treatment. These findings will set a foundation for engineering more sophisticated nanoparticle systems for imaging and manipulating genetic targets in the nucleus.},\n\tlanguage = {en},\n\tnumber = {20},\n\turldate = {2021-11-06},\n\tjournal = {Small},\n\tauthor = {Tang, Peter S. and Sathiamoorthy, Sarmitha and Lustig, Lindsay C. and Ponzielli, Romina and Inamoto, Ichiro and Penn, Linda Z. and Shin, Jumi A. and Chan, Warren C. W.},\n\tyear = {2014},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/smll.201401056},\n\tkeywords = {ligand density, nanoparticles, nuclear transport, particle size, quantum dots},\n\tpages = {4182--4192},\n\tfile = {Full Text PDF:files/2011/Tang et al. - 2014 - The Role of Ligand Density and Size in Mediating Q.pdf:application/pdf;Snapshot:files/2015/smll.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/smll.201401056-min.pdf}\n}\n\n
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\n Studying the effects of the physicochemical properties of nanomaterials on cellular uptake, toxicity, and exocytosis can provide the foundation for designing safer and more effective nanoparticles for clinical applications. However, an understanding of the effects of these properties on subcellular transport, accumulation, and distribution remains limited. The present study investigates the effects of surface density and particle size of semiconductor quantum dots on cellular uptake as well as nuclear transport kinetics, retention, and accumulation. The current work illustrates that cellular uptake and nuclear accumulation of nanoparticles depend on surface density of the nuclear localization signal (NLS) peptides with nuclear transport reaching a plateau at 20% surface NLS density in as little as 30 min. These intracellular nanoparticles have no effects on cell viability up to 72 h post treatment. These findings will set a foundation for engineering more sophisticated nanoparticle systems for imaging and manipulating genetic targets in the nucleus.\n
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\n \n\n \n \n \n \n \n \n Secreted Biomolecules Alter the Biological Identity and Cellular Interactions of Nanoparticles.\n \n \n \n \n\n\n \n Albanese, A., Walkey, C. D., Olsen, J. B., Guo, H., Emili, A., & Chan, W. C. W.\n\n\n \n\n\n\n ACS Nano, 8(6): 5515–5526. June 2014.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"SecretedPaper\n  \n \n \n \"Secreted paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{albanese_secreted_2014,\n\ttitle = {Secreted {Biomolecules} {Alter} the {Biological} {Identity} and {Cellular} {Interactions} of {Nanoparticles}},\n\tvolume = {8},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/nn4061012},\n\tdoi = {10.1021/nn4061012},\n\tabstract = {A nanoparticle’s physical and chemical properties at the time of cell contact will determine the ensuing cellular response. Aggregation and the formation of a protein corona in the extracellular environment will alter nanoparticle size, shape, and surface properties, giving it a “biological identity” that is distinct from its initial “synthetic identity”. The biological identity of a nanoparticle depends on the composition of the surrounding biological environment and determines subsequent cellular interactions. When studying nanoparticle–cell interactions, previous studies have ignored the dynamic composition of the extracellular environment as cells deplete and secrete biomolecules in a process known as “conditioning”. Here, we show that cell conditioning induces gold nanoparticle aggregation and changes the protein corona composition in a manner that depends on nanoparticle diameter, surface chemistry, and cell phenotype. The evolution of the biological identity in conditioned media enhances the cell membrane affinity, uptake, and retention of nanoparticles. These results show that dynamic extracellular environments can alter nanoparticle–cell interactions by modulating the biological identity. The effect of the dynamic nature of biological environments on the biological identity of nanoparticles must be considered to fully understand nano–bio interactions and prevent data misinterpretation.},\n\tnumber = {6},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Albanese, Alexandre and Walkey, Carl D. and Olsen, Jonathan B. and Guo, Hongbo and Emili, Andrew and Chan, Warren C. W.},\n\tmonth = jun,\n\tyear = {2014},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {5515--5526},\n\tfile = {Full Text PDF:files/2014/Albanese et al. - 2014 - Secreted Biomolecules Alter the Biological Identit.pdf:application/pdf;ACS Full Text Snapshot:files/2021/nn4061012.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nn4061012-min.pdf}\n}\n\n
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\n A nanoparticle’s physical and chemical properties at the time of cell contact will determine the ensuing cellular response. Aggregation and the formation of a protein corona in the extracellular environment will alter nanoparticle size, shape, and surface properties, giving it a “biological identity” that is distinct from its initial “synthetic identity”. The biological identity of a nanoparticle depends on the composition of the surrounding biological environment and determines subsequent cellular interactions. When studying nanoparticle–cell interactions, previous studies have ignored the dynamic composition of the extracellular environment as cells deplete and secrete biomolecules in a process known as “conditioning”. Here, we show that cell conditioning induces gold nanoparticle aggregation and changes the protein corona composition in a manner that depends on nanoparticle diameter, surface chemistry, and cell phenotype. The evolution of the biological identity in conditioned media enhances the cell membrane affinity, uptake, and retention of nanoparticles. These results show that dynamic extracellular environments can alter nanoparticle–cell interactions by modulating the biological identity. The effect of the dynamic nature of biological environments on the biological identity of nanoparticles must be considered to fully understand nano–bio interactions and prevent data misinterpretation.\n
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\n \n\n \n \n \n \n \n \n Investigating the Impact of Nanoparticle Size on Active and Passive Tumor Targeting Efficiency.\n \n \n \n \n\n\n \n Sykes, E. A., Chen, J., Zheng, G., & Chan, W. C.\n\n\n \n\n\n\n ACS Nano, 8(6): 5696–5706. June 2014.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"InvestigatingPaper\n  \n \n \n \"Investigating paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{sykes_investigating_2014,\n\ttitle = {Investigating the {Impact} of {Nanoparticle} {Size} on {Active} and {Passive} {Tumor} {Targeting} {Efficiency}},\n\tvolume = {8},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/nn500299p},\n\tdoi = {10.1021/nn500299p},\n\tabstract = {Understanding the principles governing the design of nanoparticles for tumor targeting is essential for the effective diagnosis and treatment of solid tumors. There is currently a poor understanding of how to rationally engineer nanoparticles for tumor targeting. Here, we engineered different-sized spherical gold nanoparticles to discern the effect of particle diameter on passive (poly(ethylene glycol)-coated) and active (transferrin-coated) targeting of MDA-MB-435 orthotopic tumor xenografts. Tumor accumulation of actively targeted nanoparticles was found to be 5 times faster and approximately 2-fold higher relative to their passive counterparts within the 60 nm diameter range. For 15, 30, and 100 nm, we observed no significant differences. We hypothesize that such enhancements are the result of an increased capacity to penetrate into tumors and preferentially associate with cancer cells. We also use computational modeling to explore the mechanistic parameters that can impact tumor accumulation efficacy. We demonstrate that tumor accumulation can be mediated by high nanoparticle avidity and are weakly dependent on their plasma clearance rate. Such findings suggest that empirical models can be used to rapidly screen novel nanomaterials for relative differences in tumor targeting without the need for animal work. Although our findings are specific to MDA-MB-435 tumor xenografts, our experimental and computational findings help to enrich knowledge of design considerations that will aid in the optimal engineering of spherical gold nanoparticles for cancer applications in the future.},\n\tnumber = {6},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Sykes, Edward A. and Chen, Juan and Zheng, Gang and Chan, Warren C.W.},\n\tmonth = jun,\n\tyear = {2014},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {5696--5706},\n\tfile = {Full Text PDF:files/2016/Sykes et al. - 2014 - Investigating the Impact of Nanoparticle Size on A.pdf:application/pdf;ACS Full Text Snapshot:files/2019/nn500299p.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nn500299p-min.pdf}\n}\n\n
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\n Understanding the principles governing the design of nanoparticles for tumor targeting is essential for the effective diagnosis and treatment of solid tumors. There is currently a poor understanding of how to rationally engineer nanoparticles for tumor targeting. Here, we engineered different-sized spherical gold nanoparticles to discern the effect of particle diameter on passive (poly(ethylene glycol)-coated) and active (transferrin-coated) targeting of MDA-MB-435 orthotopic tumor xenografts. Tumor accumulation of actively targeted nanoparticles was found to be 5 times faster and approximately 2-fold higher relative to their passive counterparts within the 60 nm diameter range. For 15, 30, and 100 nm, we observed no significant differences. We hypothesize that such enhancements are the result of an increased capacity to penetrate into tumors and preferentially associate with cancer cells. We also use computational modeling to explore the mechanistic parameters that can impact tumor accumulation efficacy. We demonstrate that tumor accumulation can be mediated by high nanoparticle avidity and are weakly dependent on their plasma clearance rate. Such findings suggest that empirical models can be used to rapidly screen novel nanomaterials for relative differences in tumor targeting without the need for animal work. Although our findings are specific to MDA-MB-435 tumor xenografts, our experimental and computational findings help to enrich knowledge of design considerations that will aid in the optimal engineering of spherical gold nanoparticles for cancer applications in the future.\n
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\n \n\n \n \n \n \n \n \n Real-time monitoring and control of soluble signaling factors enables enhanced progenitor cell outputs from human cord blood stem cell cultures.\n \n \n \n \n\n\n \n Csaszar, E., Chen, K., Caldwell, J., Chan, W., & Zandstra, P. W.\n\n\n \n\n\n\n Biotechnology and Bioengineering, 111(6): 1258–1264. 2014.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/bit.25163\n\n\n\n
\n\n\n\n \n \n \"Real-timePaper\n  \n \n \n \"Real-time paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{csaszar_real-time_2014,\n\ttitle = {Real-time monitoring and control of soluble signaling factors enables enhanced progenitor cell outputs from human cord blood stem cell cultures},\n\tvolume = {111},\n\tissn = {1097-0290},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/bit.25163},\n\tdoi = {10.1002/bit.25163},\n\tabstract = {Monitoring and control of primary cell cultures is challenging as they are heterogenous and dynamically complex systems. Feedback signaling proteins produced from off-target cell populations can accumulate, inhibiting the production of the desired cell populations. Although culture strategies have been developed to reduce feedback inhibition, they are typically optimized for a narrow range of process parameters and do not allow for a dynamically regulated response. Here we describe the development of a microbead-based process control system for the monitoring and control of endogenously produced signaling factors. This system uses quantum dot barcoded microbeads to assay endogenously produced signaling proteins in the culture media, allowing for the dynamic manipulation of protein concentrations. This monitoring system was incorporated into a fed-batch bioreactor to regulate the accumulation of TGF-β1 in an umbilical cord blood cell expansion system. By maintaining the concentration of TGF-β1 below an upper threshold throughout the culture, we demonstrate enhanced ex vivo expansion of hematopoietic progenitor cells at higher input cell densities and over longer culture periods. This study demonstrates the potential of a fully automated and integrated real-time control strategy in stem cell culture systems, and provides a powerful strategy to achieve highly regulated and intensified in vitro cell manufacturing systems. Biotechnol. Bioeng. 2014;111: 1258–1264. © 2013 The Authors Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2021-11-06},\n\tjournal = {Biotechnology and Bioengineering},\n\tauthor = {Csaszar, Elizabeth and Chen, Kun and Caldwell, Julia and Chan, Warren and Zandstra, Peter W.},\n\tyear = {2014},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/bit.25163},\n\tkeywords = {bioreactor, hematopoietic stem cells, process control, protein detection, soluble signaling factors},\n\tpages = {1258--1264},\n\tfile = {Full Text PDF:files/2024/Csaszar et al. - 2014 - Real-time monitoring and control of soluble signal.pdf:application/pdf;Snapshot:files/2028/bit.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/bit.25163.pdf}\n}\n\n
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\n Monitoring and control of primary cell cultures is challenging as they are heterogenous and dynamically complex systems. Feedback signaling proteins produced from off-target cell populations can accumulate, inhibiting the production of the desired cell populations. Although culture strategies have been developed to reduce feedback inhibition, they are typically optimized for a narrow range of process parameters and do not allow for a dynamically regulated response. Here we describe the development of a microbead-based process control system for the monitoring and control of endogenously produced signaling factors. This system uses quantum dot barcoded microbeads to assay endogenously produced signaling proteins in the culture media, allowing for the dynamic manipulation of protein concentrations. This monitoring system was incorporated into a fed-batch bioreactor to regulate the accumulation of TGF-β1 in an umbilical cord blood cell expansion system. By maintaining the concentration of TGF-β1 below an upper threshold throughout the culture, we demonstrate enhanced ex vivo expansion of hematopoietic progenitor cells at higher input cell densities and over longer culture periods. This study demonstrates the potential of a fully automated and integrated real-time control strategy in stem cell culture systems, and provides a powerful strategy to achieve highly regulated and intensified in vitro cell manufacturing systems. Biotechnol. Bioeng. 2014;111: 1258–1264. © 2013 The Authors Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.\n
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\n \n\n \n \n \n \n \n \n Polyethylene Glycol Backfilling Mitigates the Negative Impact of the Protein Corona on Nanoparticle Cell Targeting.\n \n \n \n \n\n\n \n Dai, Q., Walkey, C., & Chan, W. C. W.\n\n\n \n\n\n\n Angewandte Chemie International Edition, 53(20): 5093–5096. 2014.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.201309464\n\n\n\n
\n\n\n\n \n \n \"PolyethylenePaper\n  \n \n \n \"Polyethylene paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{dai_polyethylene_2014,\n\ttitle = {Polyethylene {Glycol} {Backfilling} {Mitigates} the {Negative} {Impact} of the {Protein} {Corona} on {Nanoparticle} {Cell} {Targeting}},\n\tvolume = {53},\n\tissn = {1521-3773},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201309464},\n\tdoi = {10.1002/anie.201309464},\n\tabstract = {In protein-rich environments such as the blood, the formation of a protein corona on receptor-targeting nanoparticles prevents target recognition. As a result, the ability of targeted nanoparticles to selectively bind to diseased cells is drastically inhibited. Backfilling the surface of a targeted nanoparticle with polyethylene glycol (PEG) molecules is demonstrated to reduce the formation of the protein corona and re-establishes specific binding. The length of the backfilled PEG molecules must be less than the length of the ligand linker; otherwise, PEG interferes with the binding of the targeting ligand to its corresponding cellular receptor.},\n\tlanguage = {en},\n\tnumber = {20},\n\turldate = {2021-11-06},\n\tjournal = {Angewandte Chemie International Edition},\n\tauthor = {Dai, Qin and Walkey, Carl and Chan, Warren C. W.},\n\tyear = {2014},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.201309464},\n\tkeywords = {cell targeting, nanoparticles, PEGylation, polymers, surface chemistry},\n\tpages = {5093--5096},\n\tfile = {Full Text PDF:files/2025/Dai et al. - 2014 - Polyethylene Glycol Backfilling Mitigates the Nega.pdf:application/pdf;Snapshot:files/2029/anie.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/anie.201309464.pdf}\n}\n\n
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\n\n\n
\n In protein-rich environments such as the blood, the formation of a protein corona on receptor-targeting nanoparticles prevents target recognition. As a result, the ability of targeted nanoparticles to selectively bind to diseased cells is drastically inhibited. Backfilling the surface of a targeted nanoparticle with polyethylene glycol (PEG) molecules is demonstrated to reduce the formation of the protein corona and re-establishes specific binding. The length of the backfilled PEG molecules must be less than the length of the ligand linker; otherwise, PEG interferes with the binding of the targeting ligand to its corresponding cellular receptor.\n
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\n \n\n \n \n \n \n \n \n A Call for Clinical Studies.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n ACS Nano, 8(5): 4055–4057. May 2014.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"APaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{noauthor_call_2014,\n\ttitle = {A {Call} for {Clinical} {Studies}},\n\tvolume = {8},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/nn5026466},\n\tdoi = {10.1021/nn5026466},\n\tnumber = {5},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tmonth = may,\n\tyear = {2014},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {4055--4057},\n\tfile = {Full Text PDF:files/2026/2014 - A Call for Clinical Studies.pdf:application/pdf;ACS Full Text Snapshot:files/2033/nn5026466.html:text/html},\n}\n\n
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\n \n\n \n \n \n \n \n \n Nanoparticle exposure in animals can be visualized in the skin and analysed via skin biopsy.\n \n \n \n \n\n\n \n Sykes, E. A., Dai, Q., Tsoi, K. M., Hwang, D. M., & Chan, W. C. W.\n\n\n \n\n\n\n Nat Commun, 5(1): 3796. May 2014.\n Bandiera_abtest: a Cg_type: Nature Research Journals Number: 1 Primary_atype: Research Publisher: Nature Publishing Group Subject_term: Medical research;Nanotoxicology Subject_term_id: medical-research;nanotoxicology\n\n\n\n
\n\n\n\n \n \n \"NanoparticlePaper\n  \n \n \n \"Nanoparticle paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n\n\n\n
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@article{sykes_nanoparticle_2014,\n\ttitle = {Nanoparticle exposure in animals can be visualized in the skin and analysed via skin biopsy},\n\tvolume = {5},\n\tcopyright = {2014 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},\n\tissn = {2041-1723},\n\turl = {https://www.nature.com/articles/ncomms4796},\n\tdoi = {10.1038/ncomms4796},\n\tabstract = {The increasing use of nanomaterials raises concerns about the long-term effects of chronic nanoparticle exposure on human health. However, nanoparticle exposure is difficult to evaluate non-invasively using current measurement techniques. Here we show that the skin is an important site of nanoparticle accumulation following systemic administration. Mice injected with high doses of gold nanoparticles have visibly blue skin while quantum dot-treated animals fluoresce under ultraviolet excitation. More importantly, elemental analysis of excised skin correlates with the injected dose and nanoparticle accumulation in the liver and spleen. We propose that skin analysis may be a simple strategy to quantify systemic nanoparticle exposure and predict nanoparticle fate in vivo. Our results suggest that in the future, dermal accumulation may also be exploited to trigger the release of ultraviolet and visible light-sensitive therapeutics that are currently impractical in vivo due to limits in optical penetration of tissues at these wavelengths.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2021-11-06},\n\tjournal = {Nat Commun},\n\tauthor = {Sykes, Edward A. and Dai, Qin and Tsoi, Kim M. and Hwang, David M. and Chan, Warren C. W.},\n\tmonth = may,\n\tyear = {2014},\n\tnote = {Bandiera\\_abtest: a\nCg\\_type: Nature Research Journals\nNumber: 1\nPrimary\\_atype: Research\nPublisher: Nature Publishing Group\nSubject\\_term: Medical research;Nanotoxicology\nSubject\\_term\\_id: medical-research;nanotoxicology},\n\tkeywords = {Medical research, Nanotoxicology},\n\tpages = {3796},\n\tfile = {Full Text PDF:files/2030/Sykes et al. - 2014 - Nanoparticle exposure in animals can be visualized.pdf:application/pdf;Snapshot:files/2035/ncomms4796.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/ncomms4796-min.pdf}\n}\n\n
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\n The increasing use of nanomaterials raises concerns about the long-term effects of chronic nanoparticle exposure on human health. However, nanoparticle exposure is difficult to evaluate non-invasively using current measurement techniques. Here we show that the skin is an important site of nanoparticle accumulation following systemic administration. Mice injected with high doses of gold nanoparticles have visibly blue skin while quantum dot-treated animals fluoresce under ultraviolet excitation. More importantly, elemental analysis of excised skin correlates with the injected dose and nanoparticle accumulation in the liver and spleen. We propose that skin analysis may be a simple strategy to quantify systemic nanoparticle exposure and predict nanoparticle fate in vivo. Our results suggest that in the future, dermal accumulation may also be exploited to trigger the release of ultraviolet and visible light-sensitive therapeutics that are currently impractical in vivo due to limits in optical penetration of tissues at these wavelengths.\n
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\n \n\n \n \n \n \n \n \n Protein Corona Fingerprinting Predicts the Cellular Interaction of Gold and Silver Nanoparticles.\n \n \n \n \n\n\n \n Walkey, C. D., Olsen, J. B., Song, F., Liu, R., Guo, H., Olsen, D. W. H., Cohen, Y., Emili, A., & Chan, W. C. W.\n\n\n \n\n\n\n ACS Nano, 8(3): 2439–2455. March 2014.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"ProteinPaper\n  \n \n \n \"Protein paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{walkey_protein_2014,\n\ttitle = {Protein {Corona} {Fingerprinting} {Predicts} the {Cellular} {Interaction} of {Gold} and {Silver} {Nanoparticles}},\n\tvolume = {8},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/nn406018q},\n\tdoi = {10.1021/nn406018q},\n\tabstract = {Using quantitative models to predict the biological interactions of nanoparticles will accelerate the translation of nanotechnology. Here, we characterized the serum protein corona ‘fingerprint’ formed around a library of 105 surface-modified gold nanoparticles. Applying a bioinformatics-inspired approach, we developed a multivariate model that uses the protein corona fingerprint to predict cell association 50\\% more accurately than a model that uses parameters describing nanoparticle size, aggregation state, and surface charge. Our model implicates a set of hyaluronan-binding proteins as mediators of nanoparticle–cell interactions. This study establishes a framework for developing a comprehensive database of protein corona fingerprints and biological responses for multiple nanoparticle types. Such a database can be used to develop quantitative relationships that predict the biological responses to nanoparticles and will aid in uncovering the fundamental mechanisms of nano–bio interactions.},\n\tnumber = {3},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Walkey, Carl D. and Olsen, Jonathan B. and Song, Fayi and Liu, Rong and Guo, Hongbo and Olsen, D. Wesley H. and Cohen, Yoram and Emili, Andrew and Chan, Warren C. W.},\n\tmonth = mar,\n\tyear = {2014},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {2439--2455},\n\tfile = {Full Text PDF:files/2031/Walkey et al. - 2014 - Protein Corona Fingerprinting Predicts the Cellula.pdf:application/pdf;ACS Full Text Snapshot:files/2041/nn406018q.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nn406018q-min.pdf}\n}\n\n
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\n Using quantitative models to predict the biological interactions of nanoparticles will accelerate the translation of nanotechnology. Here, we characterized the serum protein corona ‘fingerprint’ formed around a library of 105 surface-modified gold nanoparticles. Applying a bioinformatics-inspired approach, we developed a multivariate model that uses the protein corona fingerprint to predict cell association 50% more accurately than a model that uses parameters describing nanoparticle size, aggregation state, and surface charge. Our model implicates a set of hyaluronan-binding proteins as mediators of nanoparticle–cell interactions. This study establishes a framework for developing a comprehensive database of protein corona fingerprints and biological responses for multiple nanoparticle types. Such a database can be used to develop quantitative relationships that predict the biological responses to nanoparticles and will aid in uncovering the fundamental mechanisms of nano–bio interactions.\n
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\n \n\n \n \n \n \n \n \n Some Food for Thought on Nanoeducation.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n ACS Nano, 8(2): 1075–1077. February 2014.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"SomePaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{noauthor_food_2014,\n\ttitle = {Some {Food} for {Thought} on {Nanoeducation}},\n\tvolume = {8},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/nn500808m},\n\tdoi = {10.1021/nn500808m},\n\tnumber = {2},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tmonth = feb,\n\tyear = {2014},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {1075--1077},\n\tfile = {Full Text PDF:files/2036/2014 - Some Food for Thought on Nanoeducation.pdf:application/pdf;ACS Full Text Snapshot:files/2039/nn500808m.html:text/html},\n}\n\n
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\n \n\n \n \n \n \n \n \n DNA assembly of nanoparticle superstructures for controlled biological delivery and elimination.\n \n \n \n \n\n\n \n Chou, L. Y. T., Zagorovsky, K., & Chan, W. C. W.\n\n\n \n\n\n\n Nature Nanotech, 9(2): 148–155. February 2014.\n Bandiera_abtest: a Cg_type: Nature Research Journals Number: 2 Primary_atype: Research Publisher: Nature Publishing Group Subject_term: Biomedical engineering;Nanobiotechnology Subject_term_id: biomedical-engineering;nanobiotechnology\n\n\n\n
\n\n\n\n \n \n \"DNAPaper\n  \n \n \n \"DNA paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n\n\n\n
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@article{chou_dna_2014,\n\ttitle = {{DNA} assembly of nanoparticle superstructures for controlled biological delivery and elimination},\n\tvolume = {9},\n\tcopyright = {2014 Nature Publishing Group},\n\tissn = {1748-3395},\n\turl = {https://www.nature.com/articles/nnano.2013.309},\n\tdoi = {10.1038/nnano.2013.309},\n\tabstract = {The assembly of nanomaterials using DNA can produce complex nanostructures, but the biological applications of these structures remain unexplored. Here, we describe the use of DNA to control the biological delivery and elimination of inorganic nanoparticles by organizing them into colloidal superstructures. The individual nanoparticles serve as building blocks, whose size, surface chemistry and assembly architecture dictate the overall superstructure design. These superstructures interact with cells and tissues as a function of their design, but subsequently degrade into building blocks that can escape biological sequestration. We demonstrate that this strategy reduces nanoparticle retention by macrophages and improves their in vivo tumour accumulation and whole-body elimination. Superstructures can be further functionalized to carry and protect imaging or therapeutic agents against enzymatic degradation. These results suggest a different strategy to engineer nanostructure interactions with biological systems and highlight new directions in the design of biodegradable and multifunctional nanomedicine.},\n\tlanguage = {en},\n\tnumber = {2},\n\turldate = {2021-11-06},\n\tjournal = {Nature Nanotech},\n\tauthor = {Chou, Leo Y. T. and Zagorovsky, Kyryl and Chan, Warren C. W.},\n\tmonth = feb,\n\tyear = {2014},\n\tnote = {Bandiera\\_abtest: a\nCg\\_type: Nature Research Journals\nNumber: 2\nPrimary\\_atype: Research\nPublisher: Nature Publishing Group\nSubject\\_term: Biomedical engineering;Nanobiotechnology\nSubject\\_term\\_id: biomedical-engineering;nanobiotechnology},\n\tkeywords = {Biomedical engineering, Nanobiotechnology},\n\tpages = {148--155},\n\tfile = {Full Text PDF:files/2042/Chou et al. - 2014 - DNA assembly of nanoparticle superstructures for c.pdf:application/pdf},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nnano.2013.309.pdf}\n}\n\n
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\n The assembly of nanomaterials using DNA can produce complex nanostructures, but the biological applications of these structures remain unexplored. Here, we describe the use of DNA to control the biological delivery and elimination of inorganic nanoparticles by organizing them into colloidal superstructures. The individual nanoparticles serve as building blocks, whose size, surface chemistry and assembly architecture dictate the overall superstructure design. These superstructures interact with cells and tissues as a function of their design, but subsequently degrade into building blocks that can escape biological sequestration. We demonstrate that this strategy reduces nanoparticle retention by macrophages and improves their in vivo tumour accumulation and whole-body elimination. Superstructures can be further functionalized to carry and protect imaging or therapeutic agents against enzymatic degradation. These results suggest a different strategy to engineer nanostructure interactions with biological systems and highlight new directions in the design of biodegradable and multifunctional nanomedicine.\n
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\n \n\n \n \n \n \n \n \n Chapter 21 - Quantum Dots for Traceable Therapeutic Delivery.\n \n \n \n \n\n\n \n Walkey, C. D., & Chan, W. C. W.\n\n\n \n\n\n\n In Chen, X., & Wong, S., editor(s), Cancer Theranostics, pages 393–417. Academic Press, Oxford, January 2014.\n \n\n\n\n
\n\n\n\n \n \n \"ChapterPaper\n  \n \n \n \"Chapter paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@incollection{walkey_chapter_2014,\n\taddress = {Oxford},\n\ttitle = {Chapter 21 - {Quantum} {Dots} for {Traceable} {Therapeutic} {Delivery}},\n\tisbn = {978-0-12-407722-5},\n\turl = {https://www.sciencedirect.com/science/article/pii/B9780124077225000219},\n\tabstract = {Photoluminescent semiconductor nanocrystals, or quantum dots (QDs), hold promise as contrast agents for the diagnosis and characterization of disease using optical imaging. Yet, the diagnostic capabilities of a QD can be extended by coupling therapeutic molecules to its surface to form a theranostic QD. Theranostic QDs act as nanoscale therapeutic delivery vehicles (NDVs), transporting therapeutic molecules selectively to their site of action, while avoiding their interaction with sensitive healthy tissues and their degradation or modification within a biological environment. The optical contrast of the nanocrystal core allows the trafficking and localization of the construct, as well as the dynamics of therapeutic release, to be monitored in a biological environment. By monitoring the therapeutic delivery process, barriers preventing effective therapeutic delivery can be identified and overcome. While theranostic QDs have demonstrated potential in proof-of-concept applications using cultured cells and small animal models, concern surrounding the toxicity of the semiconductor core has prevented their clinical translation. Engineering total body clearance or replacing the semiconductor core with a biocompatible and/or biodegradable nanomaterial prior to clinical translation may facilitate the eventual application of theranostic QDs in human patients. Even if theranostic QDs are never applied clinically, they will still be useful for elucidating the fundamental mechanisms by which NDVs interact with biological systems and in establishing structure-activity relationships to guide NDV design. This chapter explores the design, synthesis, and application of QDs for traceable therapeutic delivery using optical imaging. Emphasis is placed on the delivery of anticancer therapeutics including chemotherapeutics and small interfering RNA.},\n\tlanguage = {en},\n\turldate = {2021-11-06},\n\tbooktitle = {Cancer {Theranostics}},\n\tpublisher = {Academic Press},\n\tauthor = {Walkey, Carl D. and Chan, Warren C. W.},\n\teditor = {Chen, Xiaoyuan and Wong, Stephen},\n\tmonth = jan,\n\tyear = {2014},\n\tdoi = {10.1016/B978-0-12-407722-5.00021-9},\n\tkeywords = {Aptamers, Chemotherapy, Clinical translation, Fluorescence, FRET, Gene therapy, Microscopy, Nanomaterials, Nanomedicine, Nanoparticles, Pharmaceutical, Quantum dots, siRNA, Theranostics, Traceable drug delivery},\n\tpages = {393--417},\n\tfile = {ScienceDirect Full Text PDF:files/2043/Walkey and Chan - 2014 - Chapter 21 - Quantum Dots for Traceable Therapeuti.pdf:application/pdf},\n\turl_Paper = {https://reader.elsevier.com/reader/sd/pii/B9780124077225000219?token=526866284D49C50B002FC0914C674F5443BD472848DFC15A51E024A52BA419847F84B48942EC8AEB0BDE7396672C7D85&originRegion=us-east-1&originCreation=20220110223429}\n}\n\n
\n
\n\n\n
\n Photoluminescent semiconductor nanocrystals, or quantum dots (QDs), hold promise as contrast agents for the diagnosis and characterization of disease using optical imaging. Yet, the diagnostic capabilities of a QD can be extended by coupling therapeutic molecules to its surface to form a theranostic QD. Theranostic QDs act as nanoscale therapeutic delivery vehicles (NDVs), transporting therapeutic molecules selectively to their site of action, while avoiding their interaction with sensitive healthy tissues and their degradation or modification within a biological environment. The optical contrast of the nanocrystal core allows the trafficking and localization of the construct, as well as the dynamics of therapeutic release, to be monitored in a biological environment. By monitoring the therapeutic delivery process, barriers preventing effective therapeutic delivery can be identified and overcome. While theranostic QDs have demonstrated potential in proof-of-concept applications using cultured cells and small animal models, concern surrounding the toxicity of the semiconductor core has prevented their clinical translation. Engineering total body clearance or replacing the semiconductor core with a biocompatible and/or biodegradable nanomaterial prior to clinical translation may facilitate the eventual application of theranostic QDs in human patients. Even if theranostic QDs are never applied clinically, they will still be useful for elucidating the fundamental mechanisms by which NDVs interact with biological systems and in establishing structure-activity relationships to guide NDV design. This chapter explores the design, synthesis, and application of QDs for traceable therapeutic delivery using optical imaging. Emphasis is placed on the delivery of anticancer therapeutics including chemotherapeutics and small interfering RNA.\n
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\n  \n 2013\n \n \n (10)\n \n \n
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\n \n \n
\n \n\n \n \n \n \n \n \n A Plasmonic DNAzyme Strategy for Point-of-Care Genetic Detection of Infectious Pathogens.\n \n \n \n \n\n\n \n Zagorovsky, K., & Chan, W. C. W.\n\n\n \n\n\n\n Angewandte Chemie International Edition, 52(11): 3168–3171. 2013.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.201208715\n\n\n\n
\n\n\n\n \n \n \"APaper\n  \n \n \n \"A paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
@article{zagorovsky_plasmonic_2013,\n\ttitle = {A {Plasmonic} {DNAzyme} {Strategy} for {Point}-of-{Care} {Genetic} {Detection} of {Infectious} {Pathogens}},\n\tvolume = {52},\n\tissn = {1521-3773},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201208715},\n\tdoi = {10.1002/anie.201208715},\n\tabstract = {Always use detection: Signal amplification from DNAzymes (see scheme) was combined with gold nanoparticles (GNPs) to give a simple and sensitive colorimetric assay for various genetic targets. The assay has 50 pM sensitivity without the need for purification steps and can detect multiple targets in parallel. This was applied to rapidly detect gonorrhea, syphilis, malaria, and hepatitis B infections.},\n\tnumber = {11},\n\turldate = {2021-11-06},\n\tjournal = {Angewandte Chemie International Edition},\n\tauthor = {Zagorovsky, Kyryl and Chan, Warren C. W.},\n\tyear = {2013},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.201208715},\n\tkeywords = {biosensors, DNA recognition, DNAzymes, nanoparticles, surface plasmon resonance},\n\tpages = {3168--3171},\n\tfile = {Full Text PDF:files/2034/Zagorovsky and Chan - 2013 - A Plasmonic DNAzyme Strategy for Point-of-Care Gen.pdf:application/pdf;Snapshot:files/2038/anie.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2022/01/ZAGORO1.pdf}\n}\n\n
\n
\n\n\n
\n Always use detection: Signal amplification from DNAzymes (see scheme) was combined with gold nanoparticles (GNPs) to give a simple and sensitive colorimetric assay for various genetic targets. The assay has 50 pM sensitivity without the need for purification steps and can detect multiple targets in parallel. This was applied to rapidly detect gonorrhea, syphilis, malaria, and hepatitis B infections.\n
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\n \n\n \n \n \n \n \n \n Implantable waveguides.\n \n \n \n \n\n\n \n Sykes, E. A., Albanese, A., & Chan, W. C. W.\n\n\n \n\n\n\n Nature Photon, 7(12): 940–941. December 2013.\n Bandiera_abtest: a Cg_type: Nature Research Journals Number: 12 Primary_atype: News & Views Publisher: Nature Publishing Group Subject_term: Biophotonics;Gels and hydrogels Subject_term_id: biophotonics;gels-and-hydrogels\n\n\n\n
\n\n\n\n \n \n \"ImplantablePaper\n  \n \n \n \"Implantable paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n\n\n\n
\n
@article{sykes_implantable_2013,\n\ttitle = {Implantable waveguides},\n\tvolume = {7},\n\tcopyright = {2013 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},\n\tissn = {1749-4893},\n\turl = {https://www.nature.com/articles/nphoton.2013.308},\n\tdoi = {10.1038/nphoton.2013.308},\n\tabstract = {The development of hydrogel patches that both guide light and accommodate optogenetic cells could usher in a new breed of implantable systems for in-body optical sensing and therapy.},\n\tlanguage = {en},\n\tnumber = {12},\n\turldate = {2021-11-06},\n\tjournal = {Nature Photon},\n\tauthor = {Sykes, Edward A. and Albanese, Alexandre and Chan, Warren C. W.},\n\tmonth = dec,\n\tyear = {2013},\n\tnote = {Bandiera\\_abtest: a\nCg\\_type: Nature Research Journals\nNumber: 12\nPrimary\\_atype: News \\& Views\nPublisher: Nature Publishing Group\nSubject\\_term: Biophotonics;Gels and hydrogels\nSubject\\_term\\_id: biophotonics;gels-and-hydrogels},\n\tkeywords = {Biophotonics, Gels and hydrogels},\n\tpages = {940--941},\n\tfile = {Full Text PDF:files/2045/Sykes et al. - 2013 - Implantable waveguides.pdf:application/pdf;Snapshot:files/2046/nphoton.2013.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nphoton.2013.308.pdf}\n}\n\n
\n
\n\n\n
\n The development of hydrogel patches that both guide light and accommodate optogenetic cells could usher in a new breed of implantable systems for in-body optical sensing and therapy.\n
\n\n\n
\n\n\n
\n \n\n \n \n \n \n \n \n Tumour-on-a-chip provides an optical window into nanoparticle tissue transport.\n \n \n \n \n\n\n \n Albanese, A., Lam, A. K., Sykes, E. A., Rocheleau, J. V., & Chan, W. C. W.\n\n\n \n\n\n\n Nat Commun, 4(1): 2718. October 2013.\n Bandiera_abtest: a Cg_type: Nature Research Journals Number: 1 Primary_atype: Research Publisher: Nature Publishing Group Subject_term: Microfluidics;Nanoscale materials;Nanotechnology in cancer Subject_term_id: microfluidics;nanoscale-materials;nanotechnology-in-cancer\n\n\n\n
\n\n\n\n \n \n \"Tumour-on-a-chipPaper\n  \n \n \n \"Tumour-on-a-chip paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n\n\n\n
\n
@article{albanese_tumour---chip_2013,\n\ttitle = {Tumour-on-a-chip provides an optical window into nanoparticle tissue transport},\n\tvolume = {4},\n\tcopyright = {2013 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},\n\tissn = {2041-1723},\n\turl = {https://www.nature.com/articles/ncomms3718},\n\tdoi = {10.1038/ncomms3718},\n\tabstract = {Nanomaterials are used for numerous biomedical applications, but the selection of optimal properties for maximum delivery remains challenging. Thus, there is a significant interest in elucidating the nano–bio interactions underlying tissue accumulation. To date, researchers have relied on cell culture or animal models to study nano–bio interactions. However, cell cultures lack the complexity of biological tissues and animal models are prohibitively slow and expensive. Here we report a tumour-on-a-chip system where incorporation of tumour-like spheroids into a microfluidic channel permits real-time analysis of nanoparticle (NP) accumulation at physiological flow conditions. We show that penetration of NPs into the tissue is limited by their diameter and that retention can be improved by receptor targeting. NP transport is predominantly diffusion-limited with convection improving accumulation mostly at the tissue perimeter. A murine tumour model confirms these findings and demonstrates that the tumour-on-a-chip can be useful for screening optimal NP designs prior to in vivo studies.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2021-11-06},\n\tjournal = {Nat Commun},\n\tauthor = {Albanese, Alexandre and Lam, Alan K. and Sykes, Edward A. and Rocheleau, Jonathan V. and Chan, Warren C. W.},\n\tmonth = oct,\n\tyear = {2013},\n\tnote = {Bandiera\\_abtest: a\nCg\\_type: Nature Research Journals\nNumber: 1\nPrimary\\_atype: Research\nPublisher: Nature Publishing Group\nSubject\\_term: Microfluidics;Nanoscale materials;Nanotechnology in cancer\nSubject\\_term\\_id: microfluidics;nanoscale-materials;nanotechnology-in-cancer},\n\tkeywords = {Microfluidics, Nanoscale materials, Nanotechnology in cancer},\n\tpages = {2718},\n\tfile = {Full Text PDF:files/2048/Albanese et al. - 2013 - Tumour-on-a-chip provides an optical window into n.pdf:application/pdf;Snapshot:files/2051/ncomms3718.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/ncomms3718.pdf}\n}\n\n
\n
\n\n\n
\n Nanomaterials are used for numerous biomedical applications, but the selection of optimal properties for maximum delivery remains challenging. Thus, there is a significant interest in elucidating the nano–bio interactions underlying tissue accumulation. To date, researchers have relied on cell culture or animal models to study nano–bio interactions. However, cell cultures lack the complexity of biological tissues and animal models are prohibitively slow and expensive. Here we report a tumour-on-a-chip system where incorporation of tumour-like spheroids into a microfluidic channel permits real-time analysis of nanoparticle (NP) accumulation at physiological flow conditions. We show that penetration of NPs into the tissue is limited by their diameter and that retention can be improved by receptor targeting. NP transport is predominantly diffusion-limited with convection improving accumulation mostly at the tissue perimeter. A murine tumour model confirms these findings and demonstrates that the tumour-on-a-chip can be useful for screening optimal NP designs prior to in vivo studies.\n
\n\n\n
\n\n\n
\n \n\n \n \n \n \n \n \n Fabrication of metal nanoshell quantum-dot barcodes for biomolecular detection.\n \n \n \n \n\n\n \n Chen, K., Chou, L. Y. T., Song, F., & Chan, W. C. W.\n\n\n \n\n\n\n Nano Today, 8(3): 228–234. June 2013.\n \n\n\n\n
\n\n\n\n \n \n \"FabricationPaper\n  \n \n \n \"Fabrication paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
@article{chen_fabrication_2013,\n\ttitle = {Fabrication of metal nanoshell quantum-dot barcodes for biomolecular detection},\n\tvolume = {8},\n\tissn = {1748-0132},\n\turl = {https://www.sciencedirect.com/science/article/pii/S1748013213000467},\n\tdoi = {10.1016/j.nantod.2013.04.009},\n\tabstract = {Quantum dot (QD) barcoded microbeads are a promising technology for high-throughput biodetection applications. Here we developed QD barcodes of a novel formulation to improve the bead stability, fluorescence consistency, targeting agents loading, and analytical sensitivity as well as to simplify the conjugation process. This novel formulation contains a mixed-polymer system in preparing the barcodes and a seed-mediated strategy to grow metal nanoshells on the surface of QD barcodes. The newly designed barcodes exhibited enhanced stability and a two-order improvement in analytical sensitivity compared with barcodes without any metal coating. This sensitivity enabled the barcodes to be used for multiplexed biosensing, for example, to differentiate the deadly malaria pathogen strain Plasmodium falciparum from the less lethal Plasmodium vivax specie in a single vial. Such improvements in QD barcodes properties will allow this multiplexed detection platform to emerge from academic development into broad practical applications.},\n\tlanguage = {en},\n\tnumber = {3},\n\turldate = {2021-11-06},\n\tjournal = {Nano Today},\n\tauthor = {Chen, Kun and Chou, Leo Y. T. and Song, Fayi and Chan, Warren C. W.},\n\tmonth = jun,\n\tyear = {2013},\n\tkeywords = {Biodetection, Malaria, Metal nanoshell, Multiplexing, Pathogen, Quantum dots},\n\tpages = {228--234},\n\tfile = {ScienceDirect Full Text PDF:files/2050/Chen et al. - 2013 - Fabrication of metal nanoshell quantum-dot barcode.pdf:application/pdf},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/1-s2.0-S1748013213000467-main.pdf}\n}\n\n
\n
\n\n\n
\n Quantum dot (QD) barcoded microbeads are a promising technology for high-throughput biodetection applications. Here we developed QD barcodes of a novel formulation to improve the bead stability, fluorescence consistency, targeting agents loading, and analytical sensitivity as well as to simplify the conjugation process. This novel formulation contains a mixed-polymer system in preparing the barcodes and a seed-mediated strategy to grow metal nanoshells on the surface of QD barcodes. The newly designed barcodes exhibited enhanced stability and a two-order improvement in analytical sensitivity compared with barcodes without any metal coating. This sensitivity enabled the barcodes to be used for multiplexed biosensing, for example, to differentiate the deadly malaria pathogen strain Plasmodium falciparum from the less lethal Plasmodium vivax specie in a single vial. Such improvements in QD barcodes properties will allow this multiplexed detection platform to emerge from academic development into broad practical applications.\n
\n\n\n
\n\n\n
\n \n\n \n \n \n \n \n \n Automating Quantum Dot Barcode Assays Using Microfluidics and Magnetism for the Development of a Point-of-Care Device.\n \n \n \n \n\n\n \n Gao, Y., Lam, A. W. Y., & Chan, W. C. W.\n\n\n \n\n\n\n ACS Appl. Mater. Interfaces, 5(8): 2853–2860. April 2013.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"AutomatingPaper\n  \n \n \n \"Automating paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{gao_automating_2013,\n\ttitle = {Automating {Quantum} {Dot} {Barcode} {Assays} {Using} {Microfluidics} and {Magnetism} for the {Development} of a {Point}-of-{Care} {Device}},\n\tvolume = {5},\n\tissn = {1944-8244},\n\turl = {https://doi.org/10.1021/am302633h},\n\tdoi = {10.1021/am302633h},\n\tabstract = {The impact of detecting multiple infectious diseases simultaneously at point-of-care with good sensitivity, specificity, and reproducibility would be enormous for containing the spread of diseases in both resource-limited and rich countries. Many barcoding technologies have been introduced for addressing this need as barcodes can be applied to detecting thousands of genetic and protein biomarkers simultaneously. However, the assay process is not automated and is tedious and requires skilled technicians. Barcoding technology is currently limited to use in resource-rich settings. Here we used magnetism and microfluidics technology to automate the multiple steps in a quantum dot barcode assay. The quantum dot-barcoded microbeads are sequentially (a) introduced into the chip, (b) magnetically moved to a stream containing target molecules, (c) moved back to the original stream containing secondary probes, (d) washed, and (e) finally aligned for detection. The assay requires 20 min, has a limit of detection of 1.2 nM, and can detect genetic targets for HIV, hepatitis B, and syphilis. This study provides a simple strategy to automate the entire barcode assay process and moves barcoding technologies one step closer to point-of-care applications.},\n\tnumber = {8},\n\turldate = {2021-11-06},\n\tjournal = {ACS Appl. Mater. Interfaces},\n\tauthor = {Gao, Yali and Lam, Albert W. Y. and Chan, Warren C. W.},\n\tmonth = apr,\n\tyear = {2013},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {2853--2860},\n\tfile = {Full Text PDF:files/2053/Gao et al. - 2013 - Automating Quantum Dot Barcode Assays Using Microf.pdf:application/pdf;ACS Full Text Snapshot:files/2056/am302633h.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/am302633h-min.pdf}\n}\n\n
\n
\n\n\n
\n The impact of detecting multiple infectious diseases simultaneously at point-of-care with good sensitivity, specificity, and reproducibility would be enormous for containing the spread of diseases in both resource-limited and rich countries. Many barcoding technologies have been introduced for addressing this need as barcodes can be applied to detecting thousands of genetic and protein biomarkers simultaneously. However, the assay process is not automated and is tedious and requires skilled technicians. Barcoding technology is currently limited to use in resource-rich settings. Here we used magnetism and microfluidics technology to automate the multiple steps in a quantum dot barcode assay. The quantum dot-barcoded microbeads are sequentially (a) introduced into the chip, (b) magnetically moved to a stream containing target molecules, (c) moved back to the original stream containing secondary probes, (d) washed, and (e) finally aligned for detection. The assay requires 20 min, has a limit of detection of 1.2 nM, and can detect genetic targets for HIV, hepatitis B, and syphilis. This study provides a simple strategy to automate the entire barcode assay process and moves barcoding technologies one step closer to point-of-care applications.\n
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\n \n\n \n \n \n \n \n \n Illuminating the deep.\n \n \n \n \n\n\n \n Zagorovsky, K., & Chan, W. C. W.\n\n\n \n\n\n\n Nature Mater, 12(4): 285–287. April 2013.\n Bandiera_abtest: a Cg_type: Nature Research Journals Number: 4 Primary_atype: News & Views Publisher: Nature Publishing Group Subject_term: Imaging techniques;Quantum dots Subject_term_id: imaging-techniques;quantum-dots\n\n\n\n
\n\n\n\n \n \n \"IlluminatingPaper\n  \n \n \n \"Illuminating paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n\n\n\n
\n
@article{zagorovsky_illuminating_2013,\n\ttitle = {Illuminating the deep},\n\tvolume = {12},\n\tcopyright = {2013 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},\n\tissn = {1476-4660},\n\turl = {https://www.nature.com/articles/nmat3608},\n\tdoi = {10.1038/nmat3608},\n\tabstract = {Three-photon imaging enables deeper tissue penetration in vivo, however, a lack of imaging probes has restricted its use. Now, this problem has been overcome by engineering non-toxic manganese-doped quantum dots.},\n\tlanguage = {en},\n\tnumber = {4},\n\turldate = {2021-11-06},\n\tjournal = {Nature Mater},\n\tauthor = {Zagorovsky, Kyryl and Chan, Warren C. W.},\n\tmonth = apr,\n\tyear = {2013},\n\tnote = {Bandiera\\_abtest: a\nCg\\_type: Nature Research Journals\nNumber: 4\nPrimary\\_atype: News \\& Views\nPublisher: Nature Publishing Group\nSubject\\_term: Imaging techniques;Quantum dots\nSubject\\_term\\_id: imaging-techniques;quantum-dots},\n\tkeywords = {Imaging techniques, Quantum dots},\n\tpages = {285--287},\n\tfile = {Full Text PDF:files/2058/Zagorovsky and Chan - 2013 - Illuminating the deep.pdf:application/pdf;Snapshot:files/2060/nmat3608.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nmat3608-min.pdf}\n}\n\n
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\n\n\n
\n Three-photon imaging enables deeper tissue penetration in vivo, however, a lack of imaging probes has restricted its use. Now, this problem has been overcome by engineering non-toxic manganese-doped quantum dots.\n
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\n \n\n \n \n \n \n \n \n Are Quantum Dots Toxic? Exploring the Discrepancy Between Cell Culture and Animal Studies.\n \n \n \n \n\n\n \n Tsoi, K. M., Dai, Q., Alman, B. A., & Chan, W. C. W.\n\n\n \n\n\n\n Acc. Chem. Res., 46(3): 662–671. March 2013.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"ArePaper\n  \n \n \n \"Are paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{tsoi_are_2013,\n\ttitle = {Are {Quantum} {Dots} {Toxic}? {Exploring} the {Discrepancy} {Between} {Cell} {Culture} and {Animal} {Studies}},\n\tvolume = {46},\n\tissn = {0001-4842},\n\tshorttitle = {Are {Quantum} {Dots} {Toxic}?},\n\turl = {https://doi.org/10.1021/ar300040z},\n\tdoi = {10.1021/ar300040z},\n\tabstract = {Despite significant interest in developing quantum dots (QDs) for biomedical applications, many researchers are convinced that QDs will never be used for treating patients because of their potential toxicity. The perception that QDs are toxic is rooted in two assumptions. Cadmium-containing QDs can kill cells in culture. Many researchers then assume that because QDs are toxic to cells, they must be toxic to humans. In addition, many researchers classify QDs as a homogeneous group of materials. Therefore, if CdSe QDs are harmful, they extrapolate this result to all QDs. Though unsubstantiated, these assumptions continue to drive QD research. When dosing is physiologically appropriate, QD toxicity has not been demonstrated in animal models. In addition, QDs are not uniform: each design is a unique combination of physicochemical properties that influence biological activity and toxicity. In this Account, we summarize key findings from in vitro and in vivo studies, explore the causes of the discrepancy in QD toxicological data, and provide our view of the future direction of the field.In vitro and in vivo QD studies have advanced our knowledge of cellular transport kinetics, mechanisms of QD toxicity, and biodistribution following animal injection. Cell culture experiments have shown that QDs undergo design-dependent intracellular localization and they can cause cytotoxicity by releasing free cadmium into solution and by generating free radical species. In animal experiments, QDs preferentially enter the liver and spleen following intravascular injection, undergo minimal excretion if larger than 6 nm, and appear to be safe to the animal.In vitro and in vivo studies show an apparent discrepancy with regard to toxicity. Dosing provides one explanation for these findings. Under culture conditions, a cell experiences a constant QD dose, but the in vivo QD concentration can vary, and the organ-specific dose may not be high enough to induce detectable toxicity. Because QDs are retained within animals, long-term toxicity may be a problem but has not been established.Future QD toxicity studies should be standardized and systematized because methodological variability in the current body of literature makes it difficult to compare and contrast results. We advocate the following steps for consistent, comparable toxicology data: (a) standardize dose metrics, (b) characterize QD uptake concentration, (c) identify in vitro models that reflect the cells QDs interact with in vivo, and (d) use multiple assays to determine sublethal toxicity and biocompatibility.Finally, we should ask more specific toxicological questions. For example: “At what dose are 5 nm CdSe QDs that are stabilized with mercaptoacetic acid and conjugated to the antibody herceptin toxic to HeLa cells?” rather than “Are QDs toxic?” QDs are still a long way from realizing their potential as a medical technology. Modifying the current QD toxicological research paradigm, investigating toxicity in a case-by-case manner, and improving study quality are important steps in identifying a QD formulation that is safe for human use.},\n\tnumber = {3},\n\turldate = {2021-11-06},\n\tjournal = {Acc. Chem. Res.},\n\tauthor = {Tsoi, Kim M. and Dai, Qin and Alman, Benjamin A. and Chan, Warren C. W.},\n\tmonth = mar,\n\tyear = {2013},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {662--671},\n\tfile = {Full Text PDF:files/2057/Tsoi et al. - 2013 - Are Quantum Dots Toxic Exploring the Discrepancy .pdf:application/pdf;ACS Full Text Snapshot:files/2065/ar300040z.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/ar300040z.pdf}\n}\n\n
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\n Despite significant interest in developing quantum dots (QDs) for biomedical applications, many researchers are convinced that QDs will never be used for treating patients because of their potential toxicity. The perception that QDs are toxic is rooted in two assumptions. Cadmium-containing QDs can kill cells in culture. Many researchers then assume that because QDs are toxic to cells, they must be toxic to humans. In addition, many researchers classify QDs as a homogeneous group of materials. Therefore, if CdSe QDs are harmful, they extrapolate this result to all QDs. Though unsubstantiated, these assumptions continue to drive QD research. When dosing is physiologically appropriate, QD toxicity has not been demonstrated in animal models. In addition, QDs are not uniform: each design is a unique combination of physicochemical properties that influence biological activity and toxicity. In this Account, we summarize key findings from in vitro and in vivo studies, explore the causes of the discrepancy in QD toxicological data, and provide our view of the future direction of the field.In vitro and in vivo QD studies have advanced our knowledge of cellular transport kinetics, mechanisms of QD toxicity, and biodistribution following animal injection. Cell culture experiments have shown that QDs undergo design-dependent intracellular localization and they can cause cytotoxicity by releasing free cadmium into solution and by generating free radical species. In animal experiments, QDs preferentially enter the liver and spleen following intravascular injection, undergo minimal excretion if larger than 6 nm, and appear to be safe to the animal.In vitro and in vivo studies show an apparent discrepancy with regard to toxicity. Dosing provides one explanation for these findings. Under culture conditions, a cell experiences a constant QD dose, but the in vivo QD concentration can vary, and the organ-specific dose may not be high enough to induce detectable toxicity. Because QDs are retained within animals, long-term toxicity may be a problem but has not been established.Future QD toxicity studies should be standardized and systematized because methodological variability in the current body of literature makes it difficult to compare and contrast results. We advocate the following steps for consistent, comparable toxicology data: (a) standardize dose metrics, (b) characterize QD uptake concentration, (c) identify in vitro models that reflect the cells QDs interact with in vivo, and (d) use multiple assays to determine sublethal toxicity and biocompatibility.Finally, we should ask more specific toxicological questions. For example: “At what dose are 5 nm CdSe QDs that are stabilized with mercaptoacetic acid and conjugated to the antibody herceptin toxic to HeLa cells?” rather than “Are QDs toxic?” QDs are still a long way from realizing their potential as a medical technology. Modifying the current QD toxicological research paradigm, investigating toxicity in a case-by-case manner, and improving study quality are important steps in identifying a QD formulation that is safe for human use.\n
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\n \n\n \n \n \n \n \n \n A Plasmonic DNAzyme Strategy for Point-of-Care Genetic Detection of Infectious Pathogens.\n \n \n \n \n\n\n \n Zagorovsky, K., & Chan, W. C. W.\n\n\n \n\n\n\n Angewandte Chemie International Edition, 52(11): 3168–3171. 2013.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.201208715\n\n\n\n
\n\n\n\n \n \n \"APaper\n  \n \n \n \"A paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{zagorovsky_plasmonic_2013-1,\n\ttitle = {A {Plasmonic} {DNAzyme} {Strategy} for {Point}-of-{Care} {Genetic} {Detection} of {Infectious} {Pathogens}},\n\tvolume = {52},\n\tissn = {1521-3773},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201208715},\n\tdoi = {10.1002/anie.201208715},\n\tabstract = {Always use detection: Signal amplification from DNAzymes (see scheme) was combined with gold nanoparticles (GNPs) to give a simple and sensitive colorimetric assay for various genetic targets. The assay has 50 pM sensitivity without the need for purification steps and can detect multiple targets in parallel. This was applied to rapidly detect gonorrhea, syphilis, malaria, and hepatitis B infections.},\n\tnumber = {11},\n\turldate = {2021-11-06},\n\tjournal = {Angewandte Chemie International Edition},\n\tauthor = {Zagorovsky, Kyryl and Chan, Warren C. W.},\n\tyear = {2013},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.201208715},\n\tkeywords = {biosensors, DNA recognition, DNAzymes, nanoparticles, surface plasmon resonance},\n\tpages = {3168--3171},\n\tfile = {Full Text PDF:files/2061/Zagorovsky and Chan - 2013 - A Plasmonic DNAzyme Strategy for Point-of-Care Gen.pdf:application/pdf;Snapshot:files/2064/anie.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/anie.201208715.pdf}\n}\n\n
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\n Always use detection: Signal amplification from DNAzymes (see scheme) was combined with gold nanoparticles (GNPs) to give a simple and sensitive colorimetric assay for various genetic targets. The assay has 50 pM sensitivity without the need for purification steps and can detect multiple targets in parallel. This was applied to rapidly detect gonorrhea, syphilis, malaria, and hepatitis B infections.\n
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\n \n\n \n \n \n \n \n \n Complexities abound.\n \n \n \n \n\n\n \n Chan, W. C. W.\n\n\n \n\n\n\n Nature Nanotech, 8(2): 72–73. February 2013.\n Bandiera_abtest: a Cg_type: Nature Research Journals Number: 2 Primary_atype: Correspondence Publisher: Nature Publishing Group Subject_term: Characterization and analytical techniques;Nanoscale materials Subject_term_id: characterization-and-analytical-techniques;nanoscale-materials\n\n\n\n
\n\n\n\n \n \n \"ComplexitiesPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n\n\n\n
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@article{chan_complexities_2013,\n\ttitle = {Complexities abound},\n\tvolume = {8},\n\tcopyright = {2013 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},\n\tissn = {1748-3395},\n\turl = {https://www.nature.com/articles/nnano.2013.6},\n\tdoi = {10.1038/nnano.2013.6},\n\tlanguage = {en},\n\tnumber = {2},\n\turldate = {2021-11-06},\n\tjournal = {Nature Nanotech},\n\tauthor = {Chan, Warren C. W.},\n\tmonth = feb,\n\tyear = {2013},\n\tnote = {Bandiera\\_abtest: a\nCg\\_type: Nature Research Journals\nNumber: 2\nPrimary\\_atype: Correspondence\nPublisher: Nature Publishing Group\nSubject\\_term: Characterization and analytical techniques;Nanoscale materials\nSubject\\_term\\_id: characterization-and-analytical-techniques;nanoscale-materials},\n\tkeywords = {Characterization and analytical techniques, Nanoscale materials},\n\tpages = {72--73},\n\tfile = {Full Text PDF:files/2067/Chan - 2013 - Complexities abound.pdf:application/pdf;Snapshot:files/2068/nnano.2013.html:text/html},\n}\n\n
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\n \n\n \n \n \n \n \n \n Simultaneous Quantification of Cells and Nanomaterials by Inductive-Coupled Plasma Techniques.\n \n \n \n \n\n\n \n Albanese, A., Tsoi, K. M., & Chan, W. C. W.\n\n\n \n\n\n\n J Lab Autom., 18(1): 99–104. February 2013.\n Publisher: SAGE Publications Inc\n\n\n\n
\n\n\n\n \n \n \"SimultaneousPaper\n  \n \n \n \"Simultaneous paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{albanese_simultaneous_2013,\n\ttitle = {Simultaneous {Quantification} of {Cells} and {Nanomaterials} by {Inductive}-{Coupled} {Plasma} {Techniques}},\n\tvolume = {18},\n\tissn = {2211-0682},\n\turl = {https://doi.org/10.1177/2211068212457039},\n\tdoi = {10.1177/2211068212457039},\n\tabstract = {We demonstrate that endogenous cellular magnesium levels can be used as an accurate determinant of total cell number by inductively coupled plasma techniques, increasing the throughput and reproducibility of nanoparticle-uptake studies. Uptake of either gold nanoparticles or quantum dots did not affect intracellular concentration of Mg. To demonstrate this technique, we show the decreased uptake of nano-urchins in A549 cells compared with gold nanospheres.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2021-11-06},\n\tjournal = {J Lab Autom.},\n\tauthor = {Albanese, Alexandre and Tsoi, Kim M. and Chan, Warren C. W.},\n\tmonth = feb,\n\tyear = {2013},\n\tnote = {Publisher: SAGE Publications Inc},\n\tkeywords = {cell quantification, cell uptake, cellular elemental content, gold nano-urchins, gold nanoparticles, ICP-AES},\n\tpages = {99--104},\n\tfile = {SAGE PDF Full Text:files/2087/Albanese et al. - 2013 - Simultaneous Quantification of Cells and Nanomater.pdf:application/pdf},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/2211068212457039.pdf}\n}\n\n
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\n We demonstrate that endogenous cellular magnesium levels can be used as an accurate determinant of total cell number by inductively coupled plasma techniques, increasing the throughput and reproducibility of nanoparticle-uptake studies. Uptake of either gold nanoparticles or quantum dots did not affect intracellular concentration of Mg. To demonstrate this technique, we show the decreased uptake of nano-urchins in A549 cells compared with gold nanospheres.\n
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\n \n\n \n \n \n \n \n \n We Take It Personally.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n ACS Nano, 6(12): 10417–10419. December 2012.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"WePaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{noauthor_we_2012,\n\ttitle = {We {Take} {It} {Personally}},\n\tvolume = {6},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/nn305696y},\n\tdoi = {10.1021/nn305696y},\n\tnumber = {12},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tmonth = dec,\n\tyear = {2012},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {10417--10419},\n\tfile = {Full Text PDF:files/2066/2012 - We Take It Personally.pdf:application/pdf;ACS Full Text Snapshot:files/2071/nn305696y.html:text/html},\n}\n\n
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\n \n\n \n \n \n \n \n \n Three-Color Fluorescence Cross-Correlation Spectroscopy for Analyzing Complex Nanoparticle Mixtures.\n \n \n \n \n\n\n \n Blades, M. L., Grekova, E., Wobma, H. M., Chen, K., Chan, W. C. W., & Cramb, D. T.\n\n\n \n\n\n\n Anal. Chem., 84(21): 9623–9631. November 2012.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"Three-ColorPaper\n  \n \n \n \"Three-Color paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{blades_three-color_2012,\n\ttitle = {Three-{Color} {Fluorescence} {Cross}-{Correlation} {Spectroscopy} for {Analyzing} {Complex} {Nanoparticle} {Mixtures}},\n\tvolume = {84},\n\tissn = {0003-2700},\n\turl = {https://doi.org/10.1021/ac302572k},\n\tdoi = {10.1021/ac302572k},\n\tabstract = {Further insight toward the complex association and dissociation events of macromolecules requires the development of a spectroscopic technique that can track individual components, or building blocks of these macromolecules, and the complexes which they form, in real time. Three-color fluorescence cross-correlation spectroscopy (3C-FCCS) has been shown to track assemblies of three spectrally labeled species in solution. Here, we clearly show that 3C-FCCS is capable of distinguishing beads barcoded with quantum dots from free quantum dots in the background despite the 800-to-1 difference in concentration of these two components. The validation of this spectroscopic technique in combination with the development of barcode labels would enable one to start to investigate complex association and dissociation kinetics of macromolecules and nanomaterials during the assembly process.},\n\tnumber = {21},\n\turldate = {2021-11-06},\n\tjournal = {Anal. Chem.},\n\tauthor = {Blades, Megan L. and Grekova, Ekaterina and Wobma, Holly M. and Chen, Kun and Chan, Warren C. W. and Cramb, David T.},\n\tmonth = nov,\n\tyear = {2012},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {9623--9631},\n\tfile = {Full Text PDF:files/2073/Blades et al. - 2012 - Three-Color Fluorescence Cross-Correlation Spectro.pdf:application/pdf;ACS Full Text Snapshot:files/2078/ac302572k.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/ac302572k-min.pdf}\n}\n\n
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\n Further insight toward the complex association and dissociation events of macromolecules requires the development of a spectroscopic technique that can track individual components, or building blocks of these macromolecules, and the complexes which they form, in real time. Three-color fluorescence cross-correlation spectroscopy (3C-FCCS) has been shown to track assemblies of three spectrally labeled species in solution. Here, we clearly show that 3C-FCCS is capable of distinguishing beads barcoded with quantum dots from free quantum dots in the background despite the 800-to-1 difference in concentration of these two components. The validation of this spectroscopic technique in combination with the development of barcode labels would enable one to start to investigate complex association and dissociation kinetics of macromolecules and nanomaterials during the assembly process.\n
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\n \n\n \n \n \n \n \n \n Fluorescence-Tagged Gold Nanoparticles for Rapidly Characterizing the Size-Dependent Biodistribution in Tumor Models.\n \n \n \n \n\n\n \n Chou, L. Y. T., & Chan, W. C. W.\n\n\n \n\n\n\n Advanced Healthcare Materials, 1(6): 714–721. 2012.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/adhm.201200084\n\n\n\n
\n\n\n\n \n \n \"Fluorescence-TaggedPaper\n  \n \n \n \"Fluorescence-Tagged paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
@article{chou_fluorescence-tagged_2012,\n\ttitle = {Fluorescence-{Tagged} {Gold} {Nanoparticles} for {Rapidly} {Characterizing} the {Size}-{Dependent} {Biodistribution} in {Tumor} {Models}},\n\tvolume = {1},\n\tissn = {2192-2659},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.201200084},\n\tdoi = {10.1002/adhm.201200084},\n\tabstract = {Nanoparticle vehicles may improve the delivery of contrast agents and therapeutics to diseased tissues, but their rational design is currently impeded by a lack of robust technologies to characterize their in vivo behavior in real-time. This study demonstrates that fluorescent-labeled gold nanoparticles can be optimized for in vivo detection, perform pharmacokinetic analysis of nanoparticle designs, analyze tumor extravasation, and clearance kinetics in tumor-bearing animals. This optical imaging approach is non-invasive and high-throughput. Interestingly, these fluorescent gold nanoparticles can be used for multispectral imaging to compare several nanoparticle designs simultaneously within the same animal and eliminates the host-dependent variabilities across measured data. Together these results describe a novel platform for evaluating the performance of tumor-targeting nanoparticles, and provide new insights for the design of future nanotherapeutics.},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2021-11-06},\n\tjournal = {Advanced Healthcare Materials},\n\tauthor = {Chou, Leo Y. T. and Chan, Warren C. W.},\n\tyear = {2012},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/adhm.201200084},\n\tkeywords = {drug delivery, fluorescent gold nanoparticles, multispectral imaging, nanomedicine, pharmacokinetics},\n\tpages = {714--721},\n\tfile = {Full Text PDF:files/2076/Chou and Chan - 2012 - Fluorescence-Tagged Gold Nanoparticles for Rapidly.pdf:application/pdf;Snapshot:files/2077/adhm.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/adhm.201200084.pdf}\n}\n\n
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\n Nanoparticle vehicles may improve the delivery of contrast agents and therapeutics to diseased tissues, but their rational design is currently impeded by a lack of robust technologies to characterize their in vivo behavior in real-time. This study demonstrates that fluorescent-labeled gold nanoparticles can be optimized for in vivo detection, perform pharmacokinetic analysis of nanoparticle designs, analyze tumor extravasation, and clearance kinetics in tumor-bearing animals. This optical imaging approach is non-invasive and high-throughput. Interestingly, these fluorescent gold nanoparticles can be used for multispectral imaging to compare several nanoparticle designs simultaneously within the same animal and eliminates the host-dependent variabilities across measured data. Together these results describe a novel platform for evaluating the performance of tumor-targeting nanoparticles, and provide new insights for the design of future nanotherapeutics.\n
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\n \n\n \n \n \n \n \n \n Nonblinking Plasmonic Quantum Dot Assemblies for Multiplex Biological Detection.\n \n \n \n \n\n\n \n Song, F., Tang, P. S., Durst, H., Cramb, D. T., & Chan, W. C. W.\n\n\n \n\n\n\n Angewandte Chemie, 124(35): 8903–8907. 2012.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ange.201201872\n\n\n\n
\n\n\n\n \n \n \"NonblinkingPaper\n  \n \n \n \"Nonblinking paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{song_nonblinking_2012,\n\ttitle = {Nonblinking {Plasmonic} {Quantum} {Dot} {Assemblies} for {Multiplex} {Biological} {Detection}},\n\tvolume = {124},\n\tissn = {1521-3757},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/ange.201201872},\n\tdoi = {10.1002/ange.201201872},\n\tabstract = {Schichtweise Polyelektrolyt-Abscheidung, bei der die stöchiometrische Zusammensetzung und der Abstand zwischen Quantenpunkten (QDs) und Goldnanopartikeln (GNPs) genau eingestellt wird, liefert die Titelsysteme. Die Konjugation biologischer Erkennungsmoleküle an diese Nano-Strichcodes ermöglicht eine gezielte Einschleusung in Zellen und eine verlängerte Verweilzeit bei minimaler Toxizität.},\n\tnumber = {35},\n\turldate = {2021-11-06},\n\tjournal = {Angewandte Chemie},\n\tauthor = {Song, Fayi and Tang, Peter S. and Durst, Holly and Cramb, David T. and Chan, Warren C. W.},\n\tyear = {2012},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ange.201201872},\n\tkeywords = {Fluoreszenzdetektion, Goldnanopartikel, Nano-Strichcodes, Quantenpunkte, Zellaufnahme},\n\tpages = {8903--8907},\n\tfile = {Full Text PDF:files/2079/Song et al. - 2012 - Nonblinking Plasmonic Quantum Dot Assemblies for M.pdf:application/pdf;Snapshot:files/2080/ange.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/ange.201201872.pdf}\n}\n\n
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\n Schichtweise Polyelektrolyt-Abscheidung, bei der die stöchiometrische Zusammensetzung und der Abstand zwischen Quantenpunkten (QDs) und Goldnanopartikeln (GNPs) genau eingestellt wird, liefert die Titelsysteme. Die Konjugation biologischer Erkennungsmoleküle an diese Nano-Strichcodes ermöglicht eine gezielte Einschleusung in Zellen und eine verlängerte Verweilzeit bei minimaler Toxizität.\n
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\n \n\n \n \n \n \n \n \n The Effect of Nanoparticle Size, Shape, and Surface Chemistry on Biological Systems.\n \n \n \n \n\n\n \n Albanese, A., Tang, P. S., & Chan, W. C.\n\n\n \n\n\n\n Annual Review of Biomedical Engineering, 14(1): 1–16. 2012.\n _eprint: https://doi.org/10.1146/annurev-bioeng-071811-150124\n\n\n\n
\n\n\n\n \n \n \"ThePaper\n  \n \n \n \"The paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{albanese_effect_2012,\n\ttitle = {The {Effect} of {Nanoparticle} {Size}, {Shape}, and {Surface} {Chemistry} on {Biological} {Systems}},\n\tvolume = {14},\n\turl = {https://doi.org/10.1146/annurev-bioeng-071811-150124},\n\tdoi = {10.1146/annurev-bioeng-071811-150124},\n\tabstract = {An understanding of the interactions between nanoparticles and biological systems is of significant interest. Studies aimed at correlating the properties of nanomaterials such as size, shape, chemical functionality, surface charge, and composition with biomolecular signaling, biological kinetics, transportation, and toxicity in both cell culture and animal experiments are under way. These fundamental studies will provide a foundation for engineering the next generation of nanoscale devices. Here, we provide rationales for these studies, review the current progress in studies of the interactions of nanomaterials with biological systems, and provide a perspective on the long-term implications of these findings.},\n\tnumber = {1},\n\tjournal = {Annual Review of Biomedical Engineering},\n\tauthor = {Albanese, Alexandre and Tang, Peter S. and Chan, Warren C.W.},\n\tyear = {2012},\n\tpmid = {22524388},\n\tnote = {\\_eprint: https://doi.org/10.1146/annurev-bioeng-071811-150124},\n\tpages = {1--16},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/annurev-bioeng-071811-150124.pdf}\n}\n\n
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\n An understanding of the interactions between nanoparticles and biological systems is of significant interest. Studies aimed at correlating the properties of nanomaterials such as size, shape, chemical functionality, surface charge, and composition with biomolecular signaling, biological kinetics, transportation, and toxicity in both cell culture and animal experiments are under way. These fundamental studies will provide a foundation for engineering the next generation of nanoscale devices. Here, we provide rationales for these studies, review the current progress in studies of the interactions of nanomaterials with biological systems, and provide a perspective on the long-term implications of these findings.\n
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\n \n\n \n \n \n \n \n \n No signs of illness.\n \n \n \n \n\n\n \n Chou, L. Y. T., & Chan, W. C. W.\n\n\n \n\n\n\n Nature Nanotech, 7(7): 416–417. July 2012.\n Bandiera_abtest: a Cg_type: Nature Research Journals Number: 7 Primary_atype: News & Views Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n \"NoPaper\n  \n \n \n \"No paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{chou_no_2012,\n\ttitle = {No signs of illness},\n\tvolume = {7},\n\tcopyright = {2012 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},\n\tissn = {1748-3395},\n\turl = {https://www.nature.com/articles/nnano.2012.110},\n\tdoi = {10.1038/nnano.2012.110},\n\tabstract = {Quantum dots that contain cadmium, selenium and zinc are not toxic to monkeys for periods of up to 90 days, but longer-term studies are needed to determine the ultimate fate of the heavy metals that accumulate in the organs.},\n\tlanguage = {en},\n\tnumber = {7},\n\turldate = {2021-11-06},\n\tjournal = {Nature Nanotech},\n\tauthor = {Chou, Leo Y. T. and Chan, Warren C. W.},\n\tmonth = jul,\n\tyear = {2012},\n\tnote = {Bandiera\\_abtest: a\nCg\\_type: Nature Research Journals\nNumber: 7\nPrimary\\_atype: News \\& Views\nPublisher: Nature Publishing Group},\n\tkeywords = {general, Materials Science, Nanotechnology, Nanotechnology and Microengineering},\n\tpages = {416--417},\n\tfile = {Full Text PDF:files/2084/Chou and Chan - 2012 - No signs of illness.pdf:application/pdf;Snapshot:files/2085/nnano.2012.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nnano.2012.110.pdf}\n}\n\n
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\n Quantum dots that contain cadmium, selenium and zinc are not toxic to monkeys for periods of up to 90 days, but longer-term studies are needed to determine the ultimate fate of the heavy metals that accumulate in the organs.\n
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\n \n\n \n \n \n \n \n \n Significantly Improved Analytical Sensitivity of Lateral Flow Immunoassays by Using Thermal Contrast.\n \n \n \n \n\n\n \n Qin, Z., Chan, W. C. W., Boulware, D. R., Akkin, T., Butler, E. K., & Bischof, J. C.\n\n\n \n\n\n\n Angewandte Chemie International Edition, 51(18): 4358–4361. 2012.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.201200997\n\n\n\n
\n\n\n\n \n \n \"SignificantlyPaper\n  \n \n \n \"Significantly paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{qin_significantly_2012,\n\ttitle = {Significantly {Improved} {Analytical} {Sensitivity} of {Lateral} {Flow} {Immunoassays} by {Using} {Thermal} {Contrast}},\n\tvolume = {51},\n\tissn = {1521-3773},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201200997},\n\tdoi = {10.1002/anie.201200997},\n\tabstract = {Heat beyond visual: The thermal contrast from the heating of gold nanoparticles upon laser stimulation can improve the analytical sensitivity of lateral flow assays (LFAs; see picture). A 32-fold improvement in sensitivity of an approved LFA for cryptococcal antigen (purple diamond) was shown, with the potential for further improvement by optimizing the backing material and the properties of the antibody-coated nanoparticles (red circle with blue Y).},\n\tnumber = {18},\n\turldate = {2021-11-06},\n\tjournal = {Angewandte Chemie International Edition},\n\tauthor = {Qin, Zhenpeng and Chan, Warren C. W. and Boulware, David R. and Akkin, Taner and Butler, Elissa K. and Bischof, John C.},\n\tyear = {2012},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.201200997},\n\tkeywords = {biosensors, diagnostics, immunoassays, nanoparticles, thermal contrast},\n\tpages = {4358--4361},\n\tfile = {Full Text PDF:files/2089/Qin et al. - 2012 - Significantly Improved Analytical Sensitivity of L.pdf:application/pdf;Snapshot:files/2090/anie.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/anie.201200997.pdf}\n}\n\n
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\n Heat beyond visual: The thermal contrast from the heating of gold nanoparticles upon laser stimulation can improve the analytical sensitivity of lateral flow assays (LFAs; see picture). A 32-fold improvement in sensitivity of an approved LFA for cryptococcal antigen (purple diamond) was shown, with the potential for further improvement by optimizing the backing material and the properties of the antibody-coated nanoparticles (red circle with blue Y).\n
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\n \n\n \n \n \n \n \n \n Nanoparticle Size and Surface Chemistry Determine Serum Protein Adsorption and Macrophage Uptake.\n \n \n \n \n\n\n \n Walkey, C. D., Olsen, J. B., Guo, H., Emili, A., & Chan, W. C. W.\n\n\n \n\n\n\n J. Am. Chem. Soc., 134(4): 2139–2147. February 2012.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"NanoparticlePaper\n  \n \n \n \"Nanoparticle paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 8 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{walkey_nanoparticle_2012,\n\ttitle = {Nanoparticle {Size} and {Surface} {Chemistry} {Determine} {Serum} {Protein} {Adsorption} and {Macrophage} {Uptake}},\n\tvolume = {134},\n\tissn = {0002-7863},\n\turl = {https://doi.org/10.1021/ja2084338},\n\tdoi = {10.1021/ja2084338},\n\tabstract = {Delivery and toxicity are critical issues facing nanomedicine research. Currently, there is limited understanding and connection between the physicochemical properties of a nanomaterial and its interactions with a physiological system. As a result, it remains unclear how to optimally synthesize and chemically modify nanomaterials for in vivo applications. It has been suggested that the physicochemical properties of a nanomaterial after synthesis, known as its “synthetic identity”, are not what a cell encounters in vivo. Adsorption of blood components and interactions with phagocytes can modify the size, aggregation state, and interfacial composition of a nanomaterial, giving it a distinct “biological identity”. Here, we investigate the role of size and surface chemistry in mediating serum protein adsorption to gold nanoparticles and their subsequent uptake by macrophages. Using label-free liquid chromatography tandem mass spectrometry, we find that over 70 different serum proteins are heterogeneously adsorbed to the surface of gold nanoparticles. The relative density of each of these adsorbed proteins depends on nanoparticle size and poly(ethylene glycol) grafting density. Variations in serum protein adsorption correlate with differences in the mechanism and efficiency of nanoparticle uptake by a macrophage cell line. Macrophages contribute to the poor efficiency of nanomaterial delivery into diseased tissues, redistribution of nanomaterials within the body, and potential toxicity. This study establishes principles for the rational design of clinically useful nanomaterials.},\n\tnumber = {4},\n\turldate = {2021-11-06},\n\tjournal = {J. Am. Chem. Soc.},\n\tauthor = {Walkey, Carl D. and Olsen, Jonathan B. and Guo, Hongbo and Emili, Andrew and Chan, Warren C. W.},\n\tmonth = feb,\n\tyear = {2012},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {2139--2147},\n\tfile = {Full Text PDF:files/2092/Walkey et al. - 2012 - Nanoparticle Size and Surface Chemistry Determine .pdf:application/pdf;ACS Full Text Snapshot:files/2095/ja2084338.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/ja2084338-min.pdf}\n}\n\n
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\n Delivery and toxicity are critical issues facing nanomedicine research. Currently, there is limited understanding and connection between the physicochemical properties of a nanomaterial and its interactions with a physiological system. As a result, it remains unclear how to optimally synthesize and chemically modify nanomaterials for in vivo applications. It has been suggested that the physicochemical properties of a nanomaterial after synthesis, known as its “synthetic identity”, are not what a cell encounters in vivo. Adsorption of blood components and interactions with phagocytes can modify the size, aggregation state, and interfacial composition of a nanomaterial, giving it a distinct “biological identity”. Here, we investigate the role of size and surface chemistry in mediating serum protein adsorption to gold nanoparticles and their subsequent uptake by macrophages. Using label-free liquid chromatography tandem mass spectrometry, we find that over 70 different serum proteins are heterogeneously adsorbed to the surface of gold nanoparticles. The relative density of each of these adsorbed proteins depends on nanoparticle size and poly(ethylene glycol) grafting density. Variations in serum protein adsorption correlate with differences in the mechanism and efficiency of nanoparticle uptake by a macrophage cell line. Macrophages contribute to the poor efficiency of nanomaterial delivery into diseased tissues, redistribution of nanomaterials within the body, and potential toxicity. This study establishes principles for the rational design of clinically useful nanomaterials.\n
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\n \n\n \n \n \n \n \n \n The development of direct multicolour fluorescence cross-correlation spectroscopy : Towards a new tool for tracking complex biomolecular events in real-time.\n \n \n \n \n\n\n \n M. Wobma, H., L. Blades, M., Grekova, E., L. McGuire, D., Chen, K., W. Chan, W. C., & T. Cramb, D.\n\n\n \n\n\n\n Physical Chemistry Chemical Physics, 14(10): 3290–3294. 2012.\n Publisher: Royal Society of Chemistry\n\n\n\n
\n\n\n\n \n \n \"ThePaper\n  \n \n \n \"The paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{mwobma_development_2012,\n\ttitle = {The development of direct multicolour fluorescence cross-correlation spectroscopy : {Towards} a new tool for tracking complex biomolecular events in real-time},\n\tvolume = {14},\n\tshorttitle = {The development of direct multicolour fluorescence cross-correlation spectroscopy},\n\turl = {http://pubs.rsc.org/en/content/articlelanding/2012/cp/c2cp23278b},\n\tdoi = {10.1039/C2CP23278B},\n\tlanguage = {en},\n\tnumber = {10},\n\turldate = {2021-11-06},\n\tjournal = {Physical Chemistry Chemical Physics},\n\tauthor = {M. Wobma, Holly and L. Blades, Megan and Grekova, Ekaterina and L. McGuire, Dylan and Chen, Kun and W. Chan, Warren C. and T. Cramb, David},\n\tyear = {2012},\n\tnote = {Publisher: Royal Society of Chemistry},\n\tpages = {3290--3294},\n\tfile = {Snapshot:files/2096/c2cp23278b.html:text/html;Full Text PDF:files/2097/M. Wobma et al. - 2012 - The development of direct multicolour fluorescence.pdf:application/pdf},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/c2cp23278b-min.pdf}\n}\n\n
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\n \n\n \n \n \n \n \n \n Understanding and controlling the interaction of nanomaterials with proteins in a physiological environment.\n \n \n \n \n\n\n \n D. Walkey, C., & W. Chan, W. C.\n\n\n \n\n\n\n Chemical Society Reviews, 41(7): 2780–2799. 2012.\n Publisher: Royal Society of Chemistry\n\n\n\n
\n\n\n\n \n \n \"UnderstandingPaper\n  \n \n \n \"Understanding paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{dwalkey_understanding_2012,\n\ttitle = {Understanding and controlling the interaction of nanomaterials with proteins in a physiological environment},\n\tvolume = {41},\n\turl = {http://pubs.rsc.org/en/content/articlelanding/2012/cs/c1cs15233e},\n\tdoi = {10.1039/C1CS15233E},\n\tlanguage = {en},\n\tnumber = {7},\n\turldate = {2021-11-06},\n\tjournal = {Chemical Society Reviews},\n\tauthor = {D. Walkey, Carl and W. Chan, Warren C.},\n\tyear = {2012},\n\tnote = {Publisher: Royal Society of Chemistry},\n\tpages = {2780--2799},\n\tfile = {Full Text PDF:files/2098/D. Walkey and W. Chan - 2012 - Understanding and controlling the interaction of n.pdf:application/pdf;Snapshot:files/2099/c1cs15233e.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/c1cs15233e-min.pdf}\n}\n\n
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\n  \n 2011\n \n \n (9)\n \n \n
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\n \n\n \n \n \n \n \n \n Quantum-Dot-Encoded Microbeads for Multiplexed Genetic Detection of Non-amplified DNA Samples.\n \n \n \n \n\n\n \n Gao, Y., Stanford, W. L., & Chan, W. C. W.\n\n\n \n\n\n\n Small, 7(1): 137–146. 2011.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/smll.201000909\n\n\n\n
\n\n\n\n \n \n \"Quantum-Dot-EncodedPaper\n  \n \n \n \"Quantum-Dot-Encoded paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{gao_quantum-dot-encoded_2011,\n\ttitle = {Quantum-{Dot}-{Encoded} {Microbeads} for {Multiplexed} {Genetic} {Detection} of {Non}-amplified {DNA} {Samples}},\n\tvolume = {7},\n\tissn = {1613-6829},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/smll.201000909},\n\tdoi = {10.1002/smll.201000909},\n\tabstract = {Barcoding technologies have become the basis for a new generation of molecular diagnostic platforms for measuring biomarkers in a high-throughput, rapid, and sensitive manner. Thus far, researchers have mainly focused on preparing different types of barcodes but, in order to use them optimally in genomic- and proteomic-based applications, there is a need to understand the effect of barcode and assay parameters on their performance. Herein, quantum-dot barcodes are systematically characterized for the detection of non-amplified DNA sequences. The effect of capture probes, reporter probes, and target DNA sequence lengths are studied, as well as the effect of the amount of noncomplementary sequences on the hybridization kinetics and efficiency. From DNA denaturation to signal detection, quantum-dot-barcode assays require less than one hour to detect a target DNA sequence with a linear dynamic range of 0.02–100 fmol. Three optically distinct quantum-dot barcodes are used to demonstrate the multiplexing capability of these barcodes for genomic detection. These results suggest that quantum-dot barcodes are an excellent platform for multiplex, rapid, and sensitive genetic detection.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2021-11-06},\n\tjournal = {Small},\n\tauthor = {Gao, Yali and Stanford, William L. and Chan, Warren C. W.},\n\tyear = {2011},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/smll.201000909},\n\tkeywords = {barcodes, diagnostics, genetic detection, hybridization, quantum dots},\n\tpages = {137--146},\n\tfile = {Full Text PDF:files/2102/Gao et al. - 2011 - Quantum-Dot-Encoded Microbeads for Multiplexed Gen.pdf:application/pdf;Snapshot:files/2104/smll.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/smll.201000909.pdf}\n}\n\n
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\n Barcoding technologies have become the basis for a new generation of molecular diagnostic platforms for measuring biomarkers in a high-throughput, rapid, and sensitive manner. Thus far, researchers have mainly focused on preparing different types of barcodes but, in order to use them optimally in genomic- and proteomic-based applications, there is a need to understand the effect of barcode and assay parameters on their performance. Herein, quantum-dot barcodes are systematically characterized for the detection of non-amplified DNA sequences. The effect of capture probes, reporter probes, and target DNA sequence lengths are studied, as well as the effect of the amount of noncomplementary sequences on the hybridization kinetics and efficiency. From DNA denaturation to signal detection, quantum-dot-barcode assays require less than one hour to detect a target DNA sequence with a linear dynamic range of 0.02–100 fmol. Three optically distinct quantum-dot barcodes are used to demonstrate the multiplexing capability of these barcodes for genomic detection. These results suggest that quantum-dot barcodes are an excellent platform for multiplex, rapid, and sensitive genetic detection.\n
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\n \n\n \n \n \n \n \n \n Rapid Screening of Genetic Biomarkers of Infectious Agents Using Quantum Dot Barcodes.\n \n \n \n \n\n\n \n Giri, S., Sykes, E. A., Jennings, T. L., & Chan, W. C. W.\n\n\n \n\n\n\n ACS Nano, 5(3): 1580–1587. March 2011.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"RapidPaper\n  \n \n \n \"Rapid paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{giri_rapid_2011,\n\ttitle = {Rapid {Screening} of {Genetic} {Biomarkers} of {Infectious} {Agents} {Using} {Quantum} {Dot} {Barcodes}},\n\tvolume = {5},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/nn102873w},\n\tdoi = {10.1021/nn102873w},\n\tabstract = {The development of a rapid and sensitive infectious disease diagnostic platform would enable one to select proper treatment and to contain the spread of the disease. Here we examined the feasibility of using quantum dot (QD) barcodes to detect genetic biomarkers of the bloodborne pathogens HIV, malaria, hepatitis B and C, and syphilis. The genetic fragments from these pathogens were detected in less than 10 min at a sample volume of 200 μL and with a detection limit in the femtomol range. A next step for the advancement of QD barcode technology to the clinic will require validation of the technology with human samples to assess for matrix effects, head-to-head comparison with existing detection method, development of techniques to automate the assay and detection process, and simplification of analytical device for the read-out of the barcode signal. Our study provides an important intermediate step in the translation of QD barcode technology for screening infectious disease agents in the developed and developing world.},\n\tnumber = {3},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Giri, Supratim and Sykes, Edward A. and Jennings, Travis L. and Chan, Warren C. W.},\n\tmonth = mar,\n\tyear = {2011},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {1580--1587},\n\tfile = {Full Text PDF:files/2103/Giri et al. - 2011 - Rapid Screening of Genetic Biomarkers of Infectiou.pdf:application/pdf;ACS Full Text Snapshot:files/2107/nn102873w.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nn102873w.pdf}\n}\n\n
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\n The development of a rapid and sensitive infectious disease diagnostic platform would enable one to select proper treatment and to contain the spread of the disease. Here we examined the feasibility of using quantum dot (QD) barcodes to detect genetic biomarkers of the bloodborne pathogens HIV, malaria, hepatitis B and C, and syphilis. The genetic fragments from these pathogens were detected in less than 10 min at a sample volume of 200 μL and with a detection limit in the femtomol range. A next step for the advancement of QD barcode technology to the clinic will require validation of the technology with human samples to assess for matrix effects, head-to-head comparison with existing detection method, development of techniques to automate the assay and detection process, and simplification of analytical device for the read-out of the barcode signal. Our study provides an important intermediate step in the translation of QD barcode technology for screening infectious disease agents in the developed and developing world.\n
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\n \n\n \n \n \n \n \n \n Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents.\n \n \n \n \n\n\n \n Lovell, J. F., Jin, C. S., Huynh, E., Jin, H., Kim, C., Rubinstein, J. L., Chan, W. C. W., Cao, W., Wang, L. V., & Zheng, G.\n\n\n \n\n\n\n Nature Mater, 10(4): 324–332. April 2011.\n Bandiera_abtest: a Cg_type: Nature Research Journals Number: 4 Primary_atype: Research Publisher: Nature Publishing Group Subject_term: Biomedical materials;Imaging techniques;Nanoscale materials Subject_term_id: biomedical-materials;imaging-techniques;nanoscale-materials\n\n\n\n
\n\n\n\n \n \n \"PorphysomePaper\n  \n \n \n \"Porphysome paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n\n\n\n
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@article{lovell_porphysome_2011,\n\ttitle = {Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents},\n\tvolume = {10},\n\tcopyright = {2011 Nature Publishing Group},\n\tissn = {1476-4660},\n\turl = {https://www.nature.com/articles/nmat2986},\n\tdoi = {10.1038/nmat2986},\n\tabstract = {Optically active nanomaterials promise to advance a range of biophotonic techniques through nanoscale optical effects and integration of multiple imaging and therapeutic modalities. Here, we report the development of porphysomes; nanovesicles formed from self-assembled porphyrin bilayers that generated large, tunable extinction coefficients, structure-dependent fluorescence self-quenching and unique photothermal and photoacoustic properties. Porphysomes enabled the sensitive visualization of lymphatic systems using photoacoustic tomography. Near-infrared fluorescence generation could be restored on dissociation, creating opportunities for low-background fluorescence imaging. As a result of their organic nature, porphysomes were enzymatically biodegradable and induced minimal acute toxicity in mice with intravenous doses of 1,000 mg kg−1. In a similar manner to liposomes, the large aqueous core of porphysomes could be passively or actively loaded. Following systemic administration, porphysomes accumulated in tumours of xenograft-bearing mice and laser irradiation induced photothermal tumour ablation. The optical properties and biocompatibility of porphysomes demonstrate the multimodal potential of organic nanoparticles for biophotonic imaging and therapy.},\n\tlanguage = {en},\n\tnumber = {4},\n\turldate = {2021-11-06},\n\tjournal = {Nature Mater},\n\tauthor = {Lovell, Jonathan F. and Jin, Cheng S. and Huynh, Elizabeth and Jin, Honglin and Kim, Chulhong and Rubinstein, John L. and Chan, Warren C. W. and Cao, Weiguo and Wang, Lihong V. and Zheng, Gang},\n\tmonth = apr,\n\tyear = {2011},\n\tnote = {Bandiera\\_abtest: a\nCg\\_type: Nature Research Journals\nNumber: 4\nPrimary\\_atype: Research\nPublisher: Nature Publishing Group\nSubject\\_term: Biomedical materials;Imaging techniques;Nanoscale materials\nSubject\\_term\\_id: biomedical-materials;imaging-techniques;nanoscale-materials},\n\tkeywords = {Biomedical materials, Imaging techniques, Nanoscale materials},\n\tpages = {324--332},\n\tfile = {Full Text PDF:files/2109/Lovell et al. - 2011 - Porphysome nanovesicles generated by porphyrin bil.pdf:application/pdf;Snapshot:files/2111/nmat2986.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nmat2986.pdf}\n}\n\n
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\n Optically active nanomaterials promise to advance a range of biophotonic techniques through nanoscale optical effects and integration of multiple imaging and therapeutic modalities. Here, we report the development of porphysomes; nanovesicles formed from self-assembled porphyrin bilayers that generated large, tunable extinction coefficients, structure-dependent fluorescence self-quenching and unique photothermal and photoacoustic properties. Porphysomes enabled the sensitive visualization of lymphatic systems using photoacoustic tomography. Near-infrared fluorescence generation could be restored on dissociation, creating opportunities for low-background fluorescence imaging. As a result of their organic nature, porphysomes were enzymatically biodegradable and induced minimal acute toxicity in mice with intravenous doses of 1,000 mg kg−1. In a similar manner to liposomes, the large aqueous core of porphysomes could be passively or actively loaded. Following systemic administration, porphysomes accumulated in tumours of xenograft-bearing mice and laser irradiation induced photothermal tumour ablation. The optical properties and biocompatibility of porphysomes demonstrate the multimodal potential of organic nanoparticles for biophotonic imaging and therapy.\n
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\n \n\n \n \n \n \n \n \n Effect of Gold Nanoparticle Aggregation on Cell Uptake and Toxicity.\n \n \n \n \n\n\n \n Albanese, A., & Chan, W. C.\n\n\n \n\n\n\n ACS Nano, 5(7): 5478–5489. July 2011.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"EffectPaper\n  \n \n \n \"Effect paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{albanese_effect_2011,\n\ttitle = {Effect of {Gold} {Nanoparticle} {Aggregation} on {Cell} {Uptake} and {Toxicity}},\n\tvolume = {5},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/nn2007496},\n\tdoi = {10.1021/nn2007496},\n\tabstract = {Aggregation appears to be a ubiquitous phenomenon among all nanoparticles and its influence in mediating cellular uptake and interactions remain unclear. Here we developed a simple technique to produce transferrin-coated gold nanoparticle aggregates of different sizes and characterized their uptake and toxicity in three different cell lines. While the aggregation did not elicit a unique toxic response, the uptake patterns were different between single and aggregated nanoparticles. There was a 25\\% decrease in uptake of aggregated nanoparticles with HeLa and A549 cells in comparison to single and monodisperse nanoparticles. However, there was a 2-fold increase in MDA-MB 435 cell uptake for the largest synthesized aggregates. These contrasting results suggest that cell type and the mechanism of interactions may play a significant role. This study highlights the need to investigate the behavior of aggregates with cells on a case-by-case basis and the importance of aggregation in mediating targeting and intracellular trafficking.},\n\tnumber = {7},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Albanese, Alexandre and Chan, Warren C.W.},\n\tmonth = jul,\n\tyear = {2011},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {5478--5489},\n\tfile = {Full Text PDF:files/2110/Albanese and Chan - 2011 - Effect of Gold Nanoparticle Aggregation on Cell Up.pdf:application/pdf;ACS Full Text Snapshot:files/2114/nn2007496.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nn2007496-min.pdf}\n}\n\n
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\n Aggregation appears to be a ubiquitous phenomenon among all nanoparticles and its influence in mediating cellular uptake and interactions remain unclear. Here we developed a simple technique to produce transferrin-coated gold nanoparticle aggregates of different sizes and characterized their uptake and toxicity in three different cell lines. While the aggregation did not elicit a unique toxic response, the uptake patterns were different between single and aggregated nanoparticles. There was a 25% decrease in uptake of aggregated nanoparticles with HeLa and A549 cells in comparison to single and monodisperse nanoparticles. However, there was a 2-fold increase in MDA-MB 435 cell uptake for the largest synthesized aggregates. These contrasting results suggest that cell type and the mechanism of interactions may play a significant role. This study highlights the need to investigate the behavior of aggregates with cells on a case-by-case basis and the importance of aggregation in mediating targeting and intracellular trafficking.\n
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\n \n\n \n \n \n \n \n \n Principles of conjugating quantum dots to proteins via carbodiimide chemistry.\n \n \n \n \n\n\n \n Song, F., & Chan, W. C. W.\n\n\n \n\n\n\n , 22(49): 494006. November 2011.\n Publisher: IOP Publishing\n\n\n\n
\n\n\n\n \n \n \"PrinciplesPaper\n  \n \n \n \"Principles paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{song_principles_2011,\n\ttitle = {Principles of conjugating quantum dots to proteins via carbodiimide chemistry},\n\tvolume = {22},\n\tissn = {0957-4484},\n\turl = {https://doi.org/10.1088/0957-4484/22/49/494006},\n\tdoi = {10.1088/0957-4484/22/49/494006},\n\tabstract = {The covalent coupling of nanomaterials to bio-recognition molecules is a critical intermediate step in using nanomaterials for biology and medicine. Here we investigate the carbodiimide-mediated conjugation of fluorescent quantum dots to different proteins (e.g., immunoglobulin G, bovine serum albumin, and horseradish peroxidase). To enable these studies, we developed a simple method to isolate quantum dot bioconjugates from unconjugated quantum dots. The results show that the reactant concentrations and protein type will impact the overall number of proteins conjugated onto the surfaces of the quantum dots, homogeneity of the protein–quantum dot conjugate population, quantum efficiency, binding avidity, and enzymatic kinetics. We propose general principles that should be followed for the successful coupling of proteins to quantum dots.},\n\tlanguage = {en},\n\tnumber = {49},\n\turldate = {2021-11-06},\n\tauthor = {Song, Fayi and Chan, Warren C. W.},\n\tmonth = nov,\n\tyear = {2011},\n\tnote = {Publisher: IOP Publishing},\n\tpages = {494006},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/Song_2011_Nanotechnology_22_494006.pdf}\n}\n\n
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\n The covalent coupling of nanomaterials to bio-recognition molecules is a critical intermediate step in using nanomaterials for biology and medicine. Here we investigate the carbodiimide-mediated conjugation of fluorescent quantum dots to different proteins (e.g., immunoglobulin G, bovine serum albumin, and horseradish peroxidase). To enable these studies, we developed a simple method to isolate quantum dot bioconjugates from unconjugated quantum dots. The results show that the reactant concentrations and protein type will impact the overall number of proteins conjugated onto the surfaces of the quantum dots, homogeneity of the protein–quantum dot conjugate population, quantum efficiency, binding avidity, and enzymatic kinetics. We propose general principles that should be followed for the successful coupling of proteins to quantum dots.\n
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\n \n\n \n \n \n \n \n \n Design and potential application of PEGylated gold nanoparticles with size-dependent permeation through brain microvasculature.\n \n \n \n \n\n\n \n Etame, A. B., Smith, C. A., Chan, W. C. W., & Rutka, J. T.\n\n\n \n\n\n\n Nanomedicine: Nanotechnology, Biology and Medicine, 7(6): 992–1000. December 2011.\n \n\n\n\n
\n\n\n\n \n \n \"DesignPaper\n  \n \n \n \"Design paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{etame_design_2011,\n\ttitle = {Design and potential application of {PEGylated} gold nanoparticles with size-dependent permeation through brain microvasculature},\n\tvolume = {7},\n\tissn = {1549-9634},\n\turl = {https://www.sciencedirect.com/science/article/pii/S154996341100164X},\n\tdoi = {10.1016/j.nano.2011.04.004},\n\tabstract = {Gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provides a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood-brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, there are currently no studies that systematically examine brain microvasculature permeation of polyethylene glycol (PEG)-functionalized AuNPs. Such studies could pave the way for rationale AuNP design for passive targeting of malignant tumors. In this report we designed and characterized AuNPs with varying core particle sizes (4–24 nm) and PEG chain lengths [molecular weight 1000–10,000]. Using an in-vitro model designed to mimic the transport-permissive brain microvasculature, we demonstrate size-dependent permeation properties with respect to core particle size and PEG chain length. In general short PEG chain length (molecular weight 1000–2000) in combination with smallest core size led to optimum permeation in our model system.\nFrom the Clinical Editor\nIn this report the authors designed and characterized PEGylated gold NPs with varying core particle sizes and PEG chain lengths and demonstrate that short PEG chain length in combination with smallest core size led to optimum permeation of a blood-brain barrier model system. These findings may pave the way to optimized therapy of malignant brain tumors.},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2021-11-06},\n\tjournal = {Nanomedicine: Nanotechnology, Biology and Medicine},\n\tauthor = {Etame, Arnold B. and Smith, Christian A. and Chan, Warren C. W. and Rutka, James T.},\n\tmonth = dec,\n\tyear = {2011},\n\tkeywords = {Brain microvasculature, Brain tumors, Gold nanoparticles, Permeation, Polyethylene glycol},\n\tpages = {992--1000},\n\tfile = {ScienceDirect Full Text PDF:files/2113/Etame et al. - 2011 - Design and potential application of PEGylated gold.pdf:application/pdf},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/1-s2.0-S154996341100164X-main-1.pdf}\n}\n\n
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\n Gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provides a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood-brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, there are currently no studies that systematically examine brain microvasculature permeation of polyethylene glycol (PEG)-functionalized AuNPs. Such studies could pave the way for rationale AuNP design for passive targeting of malignant tumors. In this report we designed and characterized AuNPs with varying core particle sizes (4–24 nm) and PEG chain lengths [molecular weight 1000–10,000]. Using an in-vitro model designed to mimic the transport-permissive brain microvasculature, we demonstrate size-dependent permeation properties with respect to core particle size and PEG chain length. In general short PEG chain length (molecular weight 1000–2000) in combination with smallest core size led to optimum permeation in our model system. From the Clinical Editor In this report the authors designed and characterized PEGylated gold NPs with varying core particle sizes and PEG chain lengths and demonstrate that short PEG chain length in combination with smallest core size led to optimum permeation of a blood-brain barrier model system. These findings may pave the way to optimized therapy of malignant brain tumors.\n
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\n \n\n \n \n \n \n \n \n Strategies for the intracellular delivery of nanoparticles.\n \n \n \n \n\n\n \n T. Chou, L. Y., Ming, K., & W. Chan, W. C.\n\n\n \n\n\n\n Chemical Society Reviews, 40(1): 233–245. 2011.\n Publisher: Royal Society of Chemistry\n\n\n\n
\n\n\n\n \n \n \"StrategiesPaper\n  \n \n \n \"Strategies paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{tchou_strategies_2011,\n\ttitle = {Strategies for the intracellular delivery of nanoparticles},\n\tvolume = {40},\n\turl = {http://pubs.rsc.org/en/content/articlelanding/2011/cs/c0cs00003e},\n\tdoi = {10.1039/C0CS00003E},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2021-11-06},\n\tjournal = {Chemical Society Reviews},\n\tauthor = {T. Chou, Leo Y. and Ming, Kevin and W. Chan, Warren C.},\n\tyear = {2011},\n\tnote = {Publisher: Royal Society of Chemistry},\n\tpages = {233--245},\n\tfile = {Full Text PDF:files/2143/T. Chou et al. - 2011 - Strategies for the intracellular delivery of nanop.pdf:application/pdf;Snapshot:files/2145/c0cs00003e.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/c0cs00003e-min.pdf}\n}\n\n
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\n \n\n \n \n \n \n \n \n Engineering multifunctional magnetic- quantum dot barcodes by flow focusing.\n \n \n \n \n\n\n \n Giri, S., Li, D., & W. Chan, W. C.\n\n\n \n\n\n\n Chemical Communications, 47(14): 4195–4197. 2011.\n Publisher: Royal Society of Chemistry\n\n\n\n
\n\n\n\n \n \n \"EngineeringPaper\n  \n \n \n \"Engineering paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n  \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{giri_engineering_2011,\n\ttitle = {Engineering multifunctional magnetic- quantum dot barcodes by flow focusing},\n\tvolume = {47},\n\turl = {http://pubs.rsc.org/en/content/articlelanding/2011/cc/c0cc05336h},\n\tdoi = {10.1039/C0CC05336H},\n\tlanguage = {en},\n\tnumber = {14},\n\turldate = {2021-11-06},\n\tjournal = {Chemical Communications},\n\tauthor = {Giri, Supratim and Li, Dawei and W. Chan, Warren C.},\n\tyear = {2011},\n\tnote = {Publisher: Royal Society of Chemistry},\n\tpages = {4195--4197},\n\tfile = {Full Text PDF:files/2144/Giri et al. - 2011 - Engineering multifunctional magnetic- quantum dot .pdf:application/pdf;Snapshot:files/2146/c0cc05336h.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/c0cc05336h.pdf}\n}\n\n
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\n \n\n \n \n \n \n \n \n Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents.\n \n \n \n \n\n\n \n Lovell, J. F., Jin, C. S., Huynh, E., Jin, H., Kim, C., Rubinstein, J. L., Chan, W. C. W., Cao, W., Wang, L. V., & Zheng, G.\n\n\n \n\n\n\n Nature Mater, 10(4): 324–332. April 2011.\n Bandiera_abtest: a Cg_type: Nature Research Journals Number: 4 Primary_atype: Research Publisher: Nature Publishing Group Subject_term: Biomedical materials;Imaging techniques;Nanoscale materials Subject_term_id: biomedical-materials;imaging-techniques;nanoscale-materials\n\n\n\n
\n\n\n\n \n \n \"PorphysomePaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n\n\n\n
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@article{lovell_porphysome_2011-1,\n\ttitle = {Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents},\n\tvolume = {10},\n\tcopyright = {2011 Nature Publishing Group},\n\tissn = {1476-4660},\n\turl = {https://www.nature.com/articles/nmat2986},\n\tdoi = {10.1038/nmat2986},\n\tabstract = {Optically active nanomaterials promise to advance a range of biophotonic techniques through nanoscale optical effects and integration of multiple imaging and therapeutic modalities. Here, we report the development of porphysomes; nanovesicles formed from self-assembled porphyrin bilayers that generated large, tunable extinction coefficients, structure-dependent fluorescence self-quenching and unique photothermal and photoacoustic properties. Porphysomes enabled the sensitive visualization of lymphatic systems using photoacoustic tomography. Near-infrared fluorescence generation could be restored on dissociation, creating opportunities for low-background fluorescence imaging. As a result of their organic nature, porphysomes were enzymatically biodegradable and induced minimal acute toxicity in mice with intravenous doses of 1,000 mg kg−1. In a similar manner to liposomes, the large aqueous core of porphysomes could be passively or actively loaded. Following systemic administration, porphysomes accumulated in tumours of xenograft-bearing mice and laser irradiation induced photothermal tumour ablation. The optical properties and biocompatibility of porphysomes demonstrate the multimodal potential of organic nanoparticles for biophotonic imaging and therapy.},\n\tlanguage = {en},\n\tnumber = {4},\n\turldate = {2021-11-06},\n\tjournal = {Nature Mater},\n\tauthor = {Lovell, Jonathan F. and Jin, Cheng S. and Huynh, Elizabeth and Jin, Honglin and Kim, Chulhong and Rubinstein, John L. and Chan, Warren C. W. and Cao, Weiguo and Wang, Lihong V. and Zheng, Gang},\n\tmonth = apr,\n\tyear = {2011},\n\tnote = {Bandiera\\_abtest: a\nCg\\_type: Nature Research Journals\nNumber: 4\nPrimary\\_atype: Research\nPublisher: Nature Publishing Group\nSubject\\_term: Biomedical materials;Imaging techniques;Nanoscale materials\nSubject\\_term\\_id: biomedical-materials;imaging-techniques;nanoscale-materials},\n\tkeywords = {Biomedical materials, Imaging techniques, Nanoscale materials},\n\tpages = {324--332},\n\tfile = {Full Text PDF:files/2148/Lovell et al. - 2011 - Porphysome nanovesicles generated by porphyrin bil.pdf:application/pdf;Snapshot:files/2149/nmat2986.html:text/html},\n}\n\n
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\n Optically active nanomaterials promise to advance a range of biophotonic techniques through nanoscale optical effects and integration of multiple imaging and therapeutic modalities. Here, we report the development of porphysomes; nanovesicles formed from self-assembled porphyrin bilayers that generated large, tunable extinction coefficients, structure-dependent fluorescence self-quenching and unique photothermal and photoacoustic properties. Porphysomes enabled the sensitive visualization of lymphatic systems using photoacoustic tomography. Near-infrared fluorescence generation could be restored on dissociation, creating opportunities for low-background fluorescence imaging. As a result of their organic nature, porphysomes were enzymatically biodegradable and induced minimal acute toxicity in mice with intravenous doses of 1,000 mg kg−1. In a similar manner to liposomes, the large aqueous core of porphysomes could be passively or actively loaded. Following systemic administration, porphysomes accumulated in tumours of xenograft-bearing mice and laser irradiation induced photothermal tumour ablation. The optical properties and biocompatibility of porphysomes demonstrate the multimodal potential of organic nanoparticles for biophotonic imaging and therapy.\n
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\n \n\n \n \n \n \n \n \n Elucidating the Interactions of Nanomaterials With Biological Systems.\n \n \n \n \n\n\n \n Chan, W. C. W.\n\n\n \n\n\n\n In pages 111–112, December 2010. American Society of Mechanical Engineers Digital Collection\n \n\n\n\n
\n\n\n\n \n \n \"ElucidatingPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@inproceedings{chan_elucidating_2010,\n\ttitle = {Elucidating the {Interactions} of {Nanomaterials} {With} {Biological} {Systems}},\n\turl = {https://asmedigitalcollection.asme.org/NEMB/proceedings/NEMB2010/43925/111/346217},\n\tdoi = {10.1115/NEMB2010-13377},\n\tlanguage = {en},\n\turldate = {2021-11-06},\n\tpublisher = {American Society of Mechanical Engineers Digital Collection},\n\tauthor = {Chan, Warren C. W.},\n\tmonth = dec,\n\tyear = {2010},\n\tpages = {111--112},\n\tfile = {Snapshot:files/2119/346217.html:text/html},\n}\n\n
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\n \n\n \n \n \n \n \n \n In vivo Quantum-Dot Toxicity Assessment.\n \n \n \n \n\n\n \n Hauck, T. S., Anderson, R. E., Fischer, H. C., Newbigging, S., & Chan, W. C. W.\n\n\n \n\n\n\n Small, 6(1): 138–144. 2010.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/smll.200900626\n\n\n\n
\n\n\n\n \n \n \"InPaper\n  \n \n \n \"In paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{hauck_vivo_2010,\n\ttitle = {In vivo {Quantum}-{Dot} {Toxicity} {Assessment}},\n\tvolume = {6},\n\tissn = {1613-6829},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/smll.200900626},\n\tdoi = {10.1002/smll.200900626},\n\tabstract = {Quantum dots have potential in biomedical applications, but concerns persist about their safety. Most toxicology data is derived from in vitro studies and may not reflect in vivo responses. Here, an initial systematic animal toxicity study of CdSe–ZnS core–shell quantum dots in healthy Sprague–Dawley rats is presented. Biodistribution, animal survival, animal mass, hematology, clinical biochemistry, and organ histology are characterized at different concentrations (2.5–15.0 nmol) over short-term ({\\textless}7 days) and long-term ({\\textgreater}80 days) periods. The results show that the quantum dot formulations do not cause appreciable toxicity even after their breakdown in vivo over time. To generalize the toxicity of quantum dots in vivo, further investigations are still required. Some of these investigations include the evaluation of quantum dot composition (e.g., PbS versus CdS), surface chemistry (e.g., functionalization with amines versus carboxylic acids), size (e.g., 2 versus 6 nm), and shape (e.g., spheres versus rods), as well as the effect of contaminants and their byproducts on biodistribution behavior and toxicity. Combining the results from all of these studies will eventually lead to a conclusion regarding the issue of quantum dot toxicity.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2021-11-06},\n\tjournal = {Small},\n\tauthor = {Hauck, Tanya S. and Anderson, Robin E. and Fischer, Hans C. and Newbigging, Susan and Chan, Warren C. W.},\n\tyear = {2010},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/smll.200900626},\n\tkeywords = {biodistribution, nanostructures, quantum dots, toxicity},\n\tpages = {138--144},\n\tfile = {Full Text PDF:files/2121/Hauck et al. - 2010 - In vivo Quantum-Dot Toxicity Assessment.pdf:application/pdf;Snapshot:files/2124/smll.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/smll.200900626.pdf}\n}\n\n
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\n Quantum dots have potential in biomedical applications, but concerns persist about their safety. Most toxicology data is derived from in vitro studies and may not reflect in vivo responses. Here, an initial systematic animal toxicity study of CdSe–ZnS core–shell quantum dots in healthy Sprague–Dawley rats is presented. Biodistribution, animal survival, animal mass, hematology, clinical biochemistry, and organ histology are characterized at different concentrations (2.5–15.0 nmol) over short-term (\\textless7 days) and long-term (\\textgreater80 days) periods. The results show that the quantum dot formulations do not cause appreciable toxicity even after their breakdown in vivo over time. To generalize the toxicity of quantum dots in vivo, further investigations are still required. Some of these investigations include the evaluation of quantum dot composition (e.g., PbS versus CdS), surface chemistry (e.g., functionalization with amines versus carboxylic acids), size (e.g., 2 versus 6 nm), and shape (e.g., spheres versus rods), as well as the effect of contaminants and their byproducts on biodistribution behavior and toxicity. Combining the results from all of these studies will eventually lead to a conclusion regarding the issue of quantum dot toxicity.\n
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\n \n\n \n \n \n \n \n \n Quantum dots: Small 1/2010.\n \n \n \n \n\n\n \n Hauck, T. S., Anderson, R. E., Fischer, H. C., Newbigging, S., & Chan, W. C. W.\n\n\n \n\n\n\n Small, 6(1). 2010.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/smll.200990120\n\n\n\n
\n\n\n\n \n \n \"QuantumPaper\n  \n \n \n \"Quantum paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{hauck_quantum_2010,\n\ttitle = {Quantum dots: {Small} 1/2010},\n\tvolume = {6},\n\tissn = {1613-6829},\n\tshorttitle = {Quantum dots},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/smll.200990120},\n\tdoi = {10.1002/smll.200990120},\n\tabstract = {The cover picture shows a pathology image of a tissue from Sprague–Dawley rats exposed to quantum dots (shown as green and red glowing spheres) after intravenous injection for toxicity analysis. The results show that ZnS-capped CdSe quantum-dot formulation does not induce a toxic response to the animal, despite the slow degradation of quantum dots in vivo. Previous studies show that metabolized quantum dots are toxic to cell cultures; in contrast, these results show that the toxicity of nanoparticles in vivo may differ in vitro. By surveying different quantum-dot compositions, sizes, and surface chemistry in animal models, the toxicity of quantum dots can be determined. For more information, please read the Full Paper “In vivo Quantum–Dot Toxicity Assessment” by W. C. W. Chan et al., beginning on page 138.},\n\tnumber = {1},\n\turldate = {2021-11-06},\n\tjournal = {Small},\n\tauthor = {Hauck, Tanya S. and Anderson, Robin E. and Fischer, Hans C. and Newbigging, Susan and Chan, Warren C. W.},\n\tyear = {2010},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/smll.200990120},\n\tfile = {Full Text PDF:files/2123/Hauck et al. - 2010 - Quantum dots Small 12010.pdf:application/pdf;Snapshot:files/2126/smll.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2022/01/Hauck-et-al.-2010-Quantum-dots-Small-12010.pdf}\n}\n\n
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\n The cover picture shows a pathology image of a tissue from Sprague–Dawley rats exposed to quantum dots (shown as green and red glowing spheres) after intravenous injection for toxicity analysis. The results show that ZnS-capped CdSe quantum-dot formulation does not induce a toxic response to the animal, despite the slow degradation of quantum dots in vivo. Previous studies show that metabolized quantum dots are toxic to cell cultures; in contrast, these results show that the toxicity of nanoparticles in vivo may differ in vitro. By surveying different quantum-dot compositions, sizes, and surface chemistry in animal models, the toxicity of quantum dots can be determined. For more information, please read the Full Paper “In vivo Quantum–Dot Toxicity Assessment” by W. C. W. Chan et al., beginning on page 138.\n
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\n \n\n \n \n \n \n \n \n Nanotechnology diagnostics for infectious diseases prevalent in developing countries.\n \n \n \n \n\n\n \n Hauck, T. S., Giri, S., Gao, Y., & Chan, W. C. W.\n\n\n \n\n\n\n Advanced Drug Delivery Reviews, 62(4): 438–448. March 2010.\n \n\n\n\n
\n\n\n\n \n \n \"NanotechnologyPaper\n  \n \n \n \"Nanotechnology paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{hauck_nanotechnology_2010,\n\tseries = {Nanotechnology {Solutions} for {Infectious} {Diseases} in {Developing} {Nations}},\n\ttitle = {Nanotechnology diagnostics for infectious diseases prevalent in developing countries},\n\tvolume = {62},\n\tissn = {0169-409X},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0169409X09003561},\n\tdoi = {10.1016/j.addr.2009.11.015},\n\tabstract = {Infectious diseases are prevalent in the developing world and are one of the developing world's major sources of morbidity and mortality. While infectious diseases can initiate in a localized region, they can spread rapidly at any moment due to the ease of traveling from one part of the world to the next. This could lead to a global pandemic. One key to preventing this spread is the development of diagnostics that can quickly identify the infectious agent so that one can properly treat or in some severe cases, quarantine a patient. There have been major advances in diagnostic technologies but infectious disease diagnostics are still based on 50-year technologies that are limited by speed of analysis, need for skilled workers, poor detection threshold and inability to detect multiple strains of infectious agents. Here, we describe advances in nanotechnology and microtechnology diagnostics for infectious diseases. In these diagnostic schemes, the nanomaterials are used as labels or barcodes while microfluidic systems are used to automate the sample preparation and the assays. We describe the current state of the field and the challenges.},\n\tlanguage = {en},\n\tnumber = {4},\n\turldate = {2021-11-06},\n\tjournal = {Advanced Drug Delivery Reviews},\n\tauthor = {Hauck, Tanya S. and Giri, Supratim and Gao, Yali and Chan, Warren C. W.},\n\tmonth = mar,\n\tyear = {2010},\n\tkeywords = {Diagnostic tests, Infectious diseases, Lab on a chip, Metal nanoparticles, Microfluidics, Nanomaterials, Nanotechnology, Quantum dots},\n\tpages = {438--448},\n\tfile = {ScienceDirect Full Text PDF:files/2127/Hauck et al. - 2010 - Nanotechnology diagnostics for infectious diseases.pdf:application/pdf},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/1-s2.0-S0169409X09003561-main-min.pdf}\n}\n\n
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\n Infectious diseases are prevalent in the developing world and are one of the developing world's major sources of morbidity and mortality. While infectious diseases can initiate in a localized region, they can spread rapidly at any moment due to the ease of traveling from one part of the world to the next. This could lead to a global pandemic. One key to preventing this spread is the development of diagnostics that can quickly identify the infectious agent so that one can properly treat or in some severe cases, quarantine a patient. There have been major advances in diagnostic technologies but infectious disease diagnostics are still based on 50-year technologies that are limited by speed of analysis, need for skilled workers, poor detection threshold and inability to detect multiple strains of infectious agents. Here, we describe advances in nanotechnology and microtechnology diagnostics for infectious diseases. In these diagnostic schemes, the nanomaterials are used as labels or barcodes while microfluidic systems are used to automate the sample preparation and the assays. We describe the current state of the field and the challenges.\n
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\n \n\n \n \n \n \n \n \n Rough around the Edges: The Inflammatory Response of Microglial Cells to Spiky Nanoparticles.\n \n \n \n \n\n\n \n Albanese, A., Sykes, E. A., & Chan, W. C. W.\n\n\n \n\n\n\n ACS Nano, 4(5): 2490–2493. May 2010.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"RoughPaper\n  \n \n \n \"Rough paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{albanese_rough_2010,\n\ttitle = {Rough around the {Edges}: {The} {Inflammatory} {Response} of {Microglial} {Cells} to {Spiky} {Nanoparticles}},\n\tvolume = {4},\n\tissn = {1936-0851},\n\tshorttitle = {Rough around the {Edges}},\n\turl = {https://doi.org/10.1021/nn100776z},\n\tdoi = {10.1021/nn100776z},\n\tabstract = {The versatility of nanoparticle design has established nanotechnology as a potential “one-stop solution” to many biological and medical applications. The capacity to control nanoparticle size, shape, and surface chemistry has enabled their use as imaging contrast agents or carriers for drugs and other compounds. However, concerns of nanoparticle toxicity have surfaced that could limit their clinical translation. In order to overcome this challenge, researchers are starting to characterize how particle properties influence their interactions with biological systems. By identifying the specific nanoparticle parameters responsible for toxicity, it may be possible to engineer safer and nontoxic nanoparticles.},\n\tnumber = {5},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Albanese, Alexandre and Sykes, Edward A. and Chan, Warren C. W.},\n\tmonth = may,\n\tyear = {2010},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {2490--2493},\n\tfile = {Full Text PDF:files/2129/Albanese et al. - 2010 - Rough around the Edges The Inflammatory Response .pdf:application/pdf;ACS Full Text Snapshot:files/2134/nn100776z.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nn100776z.pdf}\n}\n\n
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\n The versatility of nanoparticle design has established nanotechnology as a potential “one-stop solution” to many biological and medical applications. The capacity to control nanoparticle size, shape, and surface chemistry has enabled their use as imaging contrast agents or carriers for drugs and other compounds. However, concerns of nanoparticle toxicity have surfaced that could limit their clinical translation. In order to overcome this challenge, researchers are starting to characterize how particle properties influence their interactions with biological systems. By identifying the specific nanoparticle parameters responsible for toxicity, it may be possible to engineer safer and nontoxic nanoparticles.\n
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\n \n\n \n \n \n \n \n \n Exploring Primary Liver Macrophages for Studying Quantum Dot Interactions with Biological Systems.\n \n \n \n \n\n\n \n Fischer, H. C., Hauck, T. S., Gómez-Aristizábal, A., & Chan, W. C. W.\n\n\n \n\n\n\n Advanced Materials, 22(23): 2520–2524. 2010.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.200904231\n\n\n\n
\n\n\n\n \n \n \"ExploringPaper\n  \n \n \n \"Exploring paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{fischer_exploring_2010,\n\ttitle = {Exploring {Primary} {Liver} {Macrophages} for {Studying} {Quantum} {Dot} {Interactions} with {Biological} {Systems}},\n\tvolume = {22},\n\tissn = {1521-4095},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/adma.200904231},\n\tdoi = {10.1002/adma.200904231},\n\tabstract = {The effect quantum dots have on primary rat macrophages is investigated, and the findings are compared to in vivo data. In vitro uptake kinetics and degradation both reflect in vivo findings; therefore, primary macrophages are shown to be an appropriate system with which to investigate cellular responses to quantum dots and other nanoparticles in order to guide in vivo studies.},\n\tnumber = {23},\n\turldate = {2021-11-06},\n\tjournal = {Advanced Materials},\n\tauthor = {Fischer, Hans C. and Hauck, Tanya S. and Gómez-Aristizábal, Alejandro and Chan, Warren C. W.},\n\tyear = {2010},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.200904231},\n\tkeywords = {Kupffer Cells, Macrophages, Nanotechnology, Nanotoxicity, Quantum Dots},\n\tpages = {2520--2524},\n\tfile = {Full Text PDF:files/2131/Fischer et al. - 2010 - Exploring Primary Liver Macrophages for Studying Q.pdf:application/pdf;Snapshot:files/2133/adma.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/adma.200904231.pdf}\n}\n\n
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\n The effect quantum dots have on primary rat macrophages is investigated, and the findings are compared to in vivo data. In vitro uptake kinetics and degradation both reflect in vivo findings; therefore, primary macrophages are shown to be an appropriate system with which to investigate cellular responses to quantum dots and other nanoparticles in order to guide in vivo studies.\n
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\n \n\n \n \n \n \n \n \n In vivo assembly of nanoparticle components to improve targeted cancer imaging.\n \n \n \n \n\n\n \n Perrault, S. D., & Chan, W. C. W.\n\n\n \n\n\n\n PNAS, 107(25): 11194–11199. June 2010.\n Publisher: National Academy of Sciences Section: Physical Sciences\n\n\n\n
\n\n\n\n \n \n \"InPaper\n  \n \n \n \"In paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{perrault_vivo_2010,\n\ttitle = {In vivo assembly of nanoparticle components to improve targeted cancer imaging},\n\tvolume = {107},\n\tissn = {0027-8424, 1091-6490},\n\turl = {http://www.pnas.org/content/107/25/11194},\n\tdoi = {10.1073/pnas.1001367107},\n\tabstract = {Many small molecular anticancer agents are often ineffective at detecting or treating cancer due to their poor pharmacokinetics. Using nanoparticles as carriers can improve this because their large size reduces clearance and improves retention within tumors, but it also slows their rate of transfer from circulation into the tumor interstitium. Here, we demonstrate an alternative strategy whereby a molecular contrast agent and engineered nanoparticle undergo in vivo molecular assembly within tumors, combining the rapid influx of the smaller and high retention of the larger component. This strategy provided rapid tumor accumulation of a fluorescent contrast agent, 16- and 8-fold faster than fluorescently labeled macromolecule or nanoparticle controls achieved. Diagnostic sensitivity was 3.0 times that of a passively targeting nanoparticle, and this improvement was achieved 3 h after injection. The advantage of the in vivo assembly approach for targeting is rapid accumulation of small molecular agents in tumors, shorter circulation time requirements, possible systemic clearance while maintaining imaging sensitivity in the tumor, and nanoparticle anchors in tumors can be utilized to alter the pharmacokinetics of contrast agents, therapeutics, and other nanoparticles. This study demonstrates molecular assembly of nanoparticles within tumors, and provides a new basis for the future design of nanomaterials for medical applications.},\n\tlanguage = {en},\n\tnumber = {25},\n\turldate = {2021-11-06},\n\tjournal = {PNAS},\n\tauthor = {Perrault, Steven D. and Chan, Warren C. W.},\n\tmonth = jun,\n\tyear = {2010},\n\tpmid = {20534561},\n\tnote = {Publisher: National Academy of Sciences\nSection: Physical Sciences},\n\tpages = {11194--11199},\n\tfile = {Full Text PDF:files/2136/Perrault and Chan - 2010 - In vivo assembly of nanoparticle components to imp.pdf:application/pdf;Snapshot:files/2140/11194.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/11194.full_.pdf}\n}\n\n
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\n Many small molecular anticancer agents are often ineffective at detecting or treating cancer due to their poor pharmacokinetics. Using nanoparticles as carriers can improve this because their large size reduces clearance and improves retention within tumors, but it also slows their rate of transfer from circulation into the tumor interstitium. Here, we demonstrate an alternative strategy whereby a molecular contrast agent and engineered nanoparticle undergo in vivo molecular assembly within tumors, combining the rapid influx of the smaller and high retention of the larger component. This strategy provided rapid tumor accumulation of a fluorescent contrast agent, 16- and 8-fold faster than fluorescently labeled macromolecule or nanoparticle controls achieved. Diagnostic sensitivity was 3.0 times that of a passively targeting nanoparticle, and this improvement was achieved 3 h after injection. The advantage of the in vivo assembly approach for targeting is rapid accumulation of small molecular agents in tumors, shorter circulation time requirements, possible systemic clearance while maintaining imaging sensitivity in the tumor, and nanoparticle anchors in tumors can be utilized to alter the pharmacokinetics of contrast agents, therapeutics, and other nanoparticles. This study demonstrates molecular assembly of nanoparticles within tumors, and provides a new basis for the future design of nanomaterials for medical applications.\n
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\n \n\n \n \n \n \n \n \n Nanomedicine.\n \n \n \n \n\n\n \n Kim, B. Y., Rutka, J. T., & Chan, W. C.\n\n\n \n\n\n\n New England Journal of Medicine, 363(25): 2434–2443. December 2010.\n Publisher: Massachusetts Medical Society _eprint: https://doi.org/10.1056/NEJMra0912273\n\n\n\n
\n\n\n\n \n \n \"NanomedicinePaper\n  \n \n \n \"Nanomedicine paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{kim_nanomedicine_2010,\n\ttitle = {Nanomedicine},\n\tvolume = {363},\n\tissn = {0028-4793},\n\turl = {https://doi.org/10.1056/NEJMra0912273},\n\tdoi = {10.1056/NEJMra0912273},\n\tabstract = {Many diseases originate from alterations in biologic processes at the molecular or nanoscale level. Mutated genes, misfolded proteins, and infections caused by viruses or bacteria can lead to cell malfunction or miscommunication, sometimes leading to life-threatening diseases. These molecules and infectious agents are nanometers in size and may be located in biologic systems that are protected by nanometer-size barriers, such as nuclear pores 9 nm in diameter. Their chemical properties, size, and shape appear to dictate the transport of molecules to specific biologic compartments and the interactions between molecules. Nanotechnology is defined as the “intentional design, characterization, production, and applications . . .},\n\tnumber = {25},\n\turldate = {2021-11-06},\n\tjournal = {New England Journal of Medicine},\n\tauthor = {Kim, Betty Y.S. and Rutka, James T. and Chan, Warren C.W.},\n\tmonth = dec,\n\tyear = {2010},\n\tpmid = {21158659},\n\tnote = {Publisher: Massachusetts Medical Society\n\\_eprint: https://doi.org/10.1056/NEJMra0912273},\n\tpages = {2434--2443},\n\tfile = {Full Text:files/2137/Kim et al. - 2010 - Nanomedicine.pdf:application/pdf;Snapshot:files/2142/nejmra0912273.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nejmra0912273.pdf}\n}\n\n
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\n Many diseases originate from alterations in biologic processes at the molecular or nanoscale level. Mutated genes, misfolded proteins, and infections caused by viruses or bacteria can lead to cell malfunction or miscommunication, sometimes leading to life-threatening diseases. These molecules and infectious agents are nanometers in size and may be located in biologic systems that are protected by nanometer-size barriers, such as nuclear pores 9 nm in diameter. Their chemical properties, size, and shape appear to dictate the transport of molecules to specific biologic compartments and the interactions between molecules. Nanotechnology is defined as the “intentional design, characterization, production, and applications . . .\n
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\n  \n 2009\n \n \n (7)\n \n \n
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\n \n\n \n \n \n \n \n \n Synthesis and Surface Modification of Highly Monodispersed, Spherical Gold Nanoparticles of 50−200 nm.\n \n \n \n \n\n\n \n Perrault, S. D., & Chan, W. C. W.\n\n\n \n\n\n\n J. Am. Chem. Soc., 131(47): 17042–17043. December 2009.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"SynthesisPaper\n  \n \n \n \"Synthesis paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{perrault_synthesis_2009,\n\ttitle = {Synthesis and {Surface} {Modification} of {Highly} {Monodispersed}, {Spherical} {Gold} {Nanoparticles} of 50−200 nm},\n\tvolume = {131},\n\tissn = {0002-7863},\n\turl = {https://doi.org/10.1021/ja907069u},\n\tdoi = {10.1021/ja907069u},\n\tabstract = {Elucidating the impact of nanoparticle size and shape on biological systems is of fundamental importance to nanotoxicology and biomedicine. Currently, the ability to determine this is limited by the lack of a model nanoparticle system having a narrow size and shape distribution over the relevant size range (2−200 nm). Hydroquinone can be used to produce 50−200 nm gold nanoparticles that are relatively monodispersed in size with nearly spherical shapes.},\n\tnumber = {47},\n\turldate = {2021-11-06},\n\tjournal = {J. Am. Chem. Soc.},\n\tauthor = {Perrault, Steven D. and Chan, Warren C. W.},\n\tmonth = dec,\n\tyear = {2009},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {17042--17043},\n\tfile = {Full Text PDF:files/2116/Perrault and Chan - 2009 - Synthesis and Surface Modification of Highly Monod.pdf:application/pdf;ACS Full Text Snapshot:files/2117/ja907069u.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/ja907069u-1.pdf}\n}\n\n
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\n Elucidating the impact of nanoparticle size and shape on biological systems is of fundamental importance to nanotoxicology and biomedicine. Currently, the ability to determine this is limited by the lack of a model nanoparticle system having a narrow size and shape distribution over the relevant size range (2−200 nm). Hydroquinone can be used to produce 50−200 nm gold nanoparticles that are relatively monodispersed in size with nearly spherical shapes.\n
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\n \n\n \n \n \n \n \n \n A Systematic Nomenclature for Codifying Engineered Nanostructures.\n \n \n \n \n\n\n \n Gentleman, D. J., & Chan, W. C. W.\n\n\n \n\n\n\n Small, 5(4): 426–431. 2009.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/smll.200800490\n\n\n\n
\n\n\n\n \n \n \"APaper\n  \n \n \n \"A paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{gentleman_systematic_2009,\n\ttitle = {A {Systematic} {Nomenclature} for {Codifying} {Engineered} {Nanostructures}},\n\tvolume = {5},\n\tissn = {1613-6829},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/smll.200800490},\n\tdoi = {10.1002/smll.200800490},\n\tabstract = {Nanotechnology's growing applications are fueled by the synthesis and engineering of a myriad nanostructures, yet there is no systematic naming or classification scheme for such materials. This lack of a coherent nomenclature is confusing the interpretation of data sets and threatens to hamper the pace of progress and risk assessment. A systematic nomenclature that encodes the overall composition, size, shape, core and ligand chemistry, and solubility of nanostructures is presented. A typographic string of minimalist field codes facilitates digital archiving and searches for desired properties. This nomenclature system could also be used for nanomaterial hazard labeling.},\n\tlanguage = {en},\n\tnumber = {4},\n\turldate = {2021-11-06},\n\tjournal = {Small},\n\tauthor = {Gentleman, Darcy J. and Chan, Warren C. W.},\n\tyear = {2009},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/smll.200800490},\n\tkeywords = {cataloging, nanostructures, nomenclature, toxicity},\n\tpages = {426--431},\n\tfile = {Full Text PDF:files/2154/Gentleman and Chan - 2009 - A Systematic Nomenclature for Codifying Engineered.pdf:application/pdf;Snapshot:files/2156/smll.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/smll.200800490.pdf}\n}\n\n
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\n Nanotechnology's growing applications are fueled by the synthesis and engineering of a myriad nanostructures, yet there is no systematic naming or classification scheme for such materials. This lack of a coherent nomenclature is confusing the interpretation of data sets and threatens to hamper the pace of progress and risk assessment. A systematic nomenclature that encodes the overall composition, size, shape, core and ligand chemistry, and solubility of nanostructures is presented. A typographic string of minimalist field codes facilitates digital archiving and searches for desired properties. This nomenclature system could also be used for nanomaterial hazard labeling.\n
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\n \n\n \n \n \n \n \n \n Probing the Interactions of Nanoparticles with Biological Systems.\n \n \n \n \n\n\n \n Chan, W. C. W.\n\n\n \n\n\n\n The FASEB Journal, 23(S1): 69.1–69.1. 2009.\n _eprint: https://faseb.onlinelibrary.wiley.com/doi/pdf/10.1096/fasebj.23.1_supplement.69.1\n\n\n\n
\n\n\n\n \n \n \"ProbingPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{chan_probing_2009,\n\ttitle = {Probing the {Interactions} of {Nanoparticles} with {Biological} {Systems}},\n\tvolume = {23},\n\tissn = {1530-6860},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.23.1_supplement.69.1},\n\tdoi = {10.1096/fasebj.23.1_supplement.69.1},\n\tabstract = {Nanoparticles have many applications in biomedical imaging, clinical diagnostics and therapeutics. Strategies that can reproducibly prepare colloidal nanoparticles of a wide range of geometries with a tight size distribution have been achieved and unique size and shape dependent optical, magnetic, electrical, and biological properties have been discovered. In spite of what has been achieved so far, a complete understanding of the interactions of cells with nanoparticles at the molecular level is lacking. This has led to the inability to rationally design nanoparticles for biomedical applications or has led to the inability to establish a definitive conclusion on the toxicity of nanomaterials. This presentation will focus on recent findings of the size and shape dependent interactions of nanoparticles with receptors on the cell surface. Specifically, data pertaining to the effect of antibody-coated gold and silver nanoparticle size on regulating membrane receptor internalization and their subsequent signaling will be discussed. The findings presented here may assist in the design of nanoscale delivery and therapeutic systems and provide insights into nanotoxicity.},\n\tlanguage = {en},\n\tnumber = {S1},\n\turldate = {2021-11-06},\n\tjournal = {The FASEB Journal},\n\tauthor = {Chan, Warren C. W.},\n\tyear = {2009},\n\tnote = {\\_eprint: https://faseb.onlinelibrary.wiley.com/doi/pdf/10.1096/fasebj.23.1\\_supplement.69.1},\n\tpages = {69.1--69.1},\n\tfile = {Snapshot:files/2159/fasebj.23.1_supplement.69.html:text/html},\n}\n\n
\n
\n\n\n
\n Nanoparticles have many applications in biomedical imaging, clinical diagnostics and therapeutics. Strategies that can reproducibly prepare colloidal nanoparticles of a wide range of geometries with a tight size distribution have been achieved and unique size and shape dependent optical, magnetic, electrical, and biological properties have been discovered. In spite of what has been achieved so far, a complete understanding of the interactions of cells with nanoparticles at the molecular level is lacking. This has led to the inability to rationally design nanoparticles for biomedical applications or has led to the inability to establish a definitive conclusion on the toxicity of nanomaterials. This presentation will focus on recent findings of the size and shape dependent interactions of nanoparticles with receptors on the cell surface. Specifically, data pertaining to the effect of antibody-coated gold and silver nanoparticle size on regulating membrane receptor internalization and their subsequent signaling will be discussed. The findings presented here may assist in the design of nanoscale delivery and therapeutic systems and provide insights into nanotoxicity.\n
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\n \n\n \n \n \n \n \n \n Mediating Tumor Targeting Efficiency of Nanoparticles Through Design.\n \n \n \n \n\n\n \n Perrault, S. D., Walkey, C., Jennings, T., Fischer, H. C., & Chan, W. C. W.\n\n\n \n\n\n\n Nano Lett., 9(5): 1909–1915. May 2009.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"MediatingPaper\n  \n \n \n \"Mediating paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{perrault_mediating_2009,\n\ttitle = {Mediating {Tumor} {Targeting} {Efficiency} of {Nanoparticles} {Through} {Design}},\n\tvolume = {9},\n\tissn = {1530-6984},\n\turl = {https://doi.org/10.1021/nl900031y},\n\tdoi = {10.1021/nl900031y},\n\tabstract = {Here we systematically examined the effect of nanoparticle size (10−100 nm) and surface chemistry (i.e., poly(ethylene glycol)) on passive targeting of tumors in vivo. We found that the physical and chemical properties of the nanoparticles influenced their pharmacokinetic behavior, which ultimately determined their tumor accumulation capacity. Interestingly, the permeation of nanoparticles within the tumor is highly dependent on the overall size of the nanoparticle, where larger nanoparticles appear to stay near the vasculature while smaller nanoparticles rapidly diffuse throughout the tumor matrix. Our results provide design parameters for engineering nanoparticles for optimized tumor targeting of contrast agents and therapeutics.},\n\tnumber = {5},\n\turldate = {2021-11-06},\n\tjournal = {Nano Lett.},\n\tauthor = {Perrault, Steven D. and Walkey, Carl and Jennings, Travis and Fischer, Hans C. and Chan, Warren C. W.},\n\tmonth = may,\n\tyear = {2009},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {1909--1915},\n\tfile = {Full Text PDF:files/2158/Perrault et al. - 2009 - Mediating Tumor Targeting Efficiency of Nanopartic.pdf:application/pdf;ACS Full Text Snapshot:files/2161/nl900031y.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nl900031y-compressed.pdf}\n}\n\n
\n
\n\n\n
\n Here we systematically examined the effect of nanoparticle size (10−100 nm) and surface chemistry (i.e., poly(ethylene glycol)) on passive targeting of tumors in vivo. We found that the physical and chemical properties of the nanoparticles influenced their pharmacokinetic behavior, which ultimately determined their tumor accumulation capacity. Interestingly, the permeation of nanoparticles within the tumor is highly dependent on the overall size of the nanoparticle, where larger nanoparticles appear to stay near the vasculature while smaller nanoparticles rapidly diffuse throughout the tumor matrix. Our results provide design parameters for engineering nanoparticles for optimized tumor targeting of contrast agents and therapeutics.\n
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\n \n\n \n \n \n \n \n \n Visualizing Quantum Dots in Biological Samples Using Silver Staining.\n \n \n \n \n\n\n \n Chou, L. Y. T., Fischer, H. C., Perrault, S. D., & Chan, W. C. W.\n\n\n \n\n\n\n Anal. Chem., 81(11): 4560–4565. June 2009.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"VisualizingPaper\n  \n \n \n \"Visualizing paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{chou_visualizing_2009,\n\ttitle = {Visualizing {Quantum} {Dots} in {Biological} {Samples} {Using} {Silver} {Staining}},\n\tvolume = {81},\n\tissn = {0003-2700},\n\turl = {https://doi.org/10.1021/ac900344a},\n\tdoi = {10.1021/ac900344a},\n\tabstract = {Quantum dot (QD) based contrast agents are currently being developed as probes for bioimaging and as vehicles for drug delivery. The ability to detect QDs, regardless of fluorescence brightness, in cells, tissues, and organs is imperative to their development. Traditional methods used to visualize the distribution of QDs in biological samples mainly rely on fluorescence imaging, which does not account for optically degenerate QDs as a result of oxidative quenching within the biological environment. Here, we demonstrate the use of silver staining for directly visualizing the distribution of QDs within biological samples under bright field microscopy. This strategy involves silver deposition onto the surface of QDs upon reduction by hydroquinone, effectively amplifying the size of QDs until visible for detection. The method can be used to detect non-fluorescent QDs and is fast, simple, and inexpensive.},\n\tnumber = {11},\n\turldate = {2021-11-06},\n\tjournal = {Anal. Chem.},\n\tauthor = {Chou, Leo Y. T. and Fischer, Hans C. and Perrault, Steve D. and Chan, Warren C. W.},\n\tmonth = jun,\n\tyear = {2009},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {4560--4565},\n\tfile = {Full Text PDF:files/2160/Chou et al. - 2009 - Visualizing Quantum Dots in Biological Samples Usi.pdf:application/pdf;ACS Full Text Snapshot:files/2162/ac900344a.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/ac900344a-min.pdf}\n}\n\n
\n
\n\n\n
\n Quantum dot (QD) based contrast agents are currently being developed as probes for bioimaging and as vehicles for drug delivery. The ability to detect QDs, regardless of fluorescence brightness, in cells, tissues, and organs is imperative to their development. Traditional methods used to visualize the distribution of QDs in biological samples mainly rely on fluorescence imaging, which does not account for optically degenerate QDs as a result of oxidative quenching within the biological environment. Here, we demonstrate the use of silver staining for directly visualizing the distribution of QDs within biological samples under bright field microscopy. This strategy involves silver deposition onto the surface of QDs upon reduction by hydroquinone, effectively amplifying the size of QDs until visible for detection. The method can be used to detect non-fluorescent QDs and is fast, simple, and inexpensive.\n
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\n \n\n \n \n \n \n \n Bio-Applications of Nanoparticles.\n \n \n \n\n\n \n Chan, W. C. W.\n\n\n \n\n\n\n Springer Science & Business Media, September 2009.\n Google-Books-ID: UEO_KgT2LdwC\n\n\n\n
\n\n\n\n \n\n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n\n\n\n
\n
@book{chan_bio-applications_2009,\n\ttitle = {Bio-{Applications} of {Nanoparticles}},\n\tisbn = {978-0-387-76713-0},\n\tabstract = {In this edited book, we highlight the central players in the Bionanotechnology field, which are the nanostructures and biomolecules. The book starts by describing how nanostructures are synthesized and by describing the wide variety of nanostructures available for biological research and applications. Also shown are the techniques used to synthesize a wide variety of biological molecules. Next, there is a focus on the assembly of nanostructures with biological molecules, which could lead to the design of multi-functional nanosystems. In the following chapters, examples of the unique properties of nanostructures are provided along with the current applications of these nanostructures in biology and medicine. Some applications include the use of gold nanoparticles in diagnostic applications, quantum dots and silica nanoparticles for imaging, and liposomes for drug delivery. In the final chapters of the book, the toxicity of nanostructures are described. This book provides broad examples of current developments in Bionanotechnology research and would be an excellent introduction to the field.},\n\tlanguage = {en},\n\tpublisher = {Springer Science \\& Business Media},\n\tauthor = {Chan, Warren C. W.},\n\tmonth = sep,\n\tyear = {2009},\n\tnote = {Google-Books-ID: UEO\\_KgT2LdwC},\n\tkeywords = {Medical / General, Medical / Pharmacology, Medical / Research},\n}\n\n
\n
\n\n\n
\n In this edited book, we highlight the central players in the Bionanotechnology field, which are the nanostructures and biomolecules. The book starts by describing how nanostructures are synthesized and by describing the wide variety of nanostructures available for biological research and applications. Also shown are the techniques used to synthesize a wide variety of biological molecules. Next, there is a focus on the assembly of nanostructures with biological molecules, which could lead to the design of multi-functional nanosystems. In the following chapters, examples of the unique properties of nanostructures are provided along with the current applications of these nanostructures in biology and medicine. Some applications include the use of gold nanoparticles in diagnostic applications, quantum dots and silica nanoparticles for imaging, and liposomes for drug delivery. In the final chapters of the book, the toxicity of nanostructures are described. This book provides broad examples of current developments in Bionanotechnology research and would be an excellent introduction to the field.\n
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\n \n\n \n \n \n \n \n \n Application of semiconductor and metal nanostructures in biology and medicine.\n \n \n \n \n\n\n \n Walkey, C., Sykes, E. A., & Chan, W. C. W.\n\n\n \n\n\n\n Hematology, 2009(1): 701–707. January 2009.\n \n\n\n\n
\n\n\n\n \n \n \"ApplicationPaper\n  \n \n \n \"Application paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{walkey_application_2009,\n\ttitle = {Application of semiconductor and metal nanostructures in biology and medicine},\n\tvolume = {2009},\n\tissn = {1520-4391},\n\turl = {https://doi.org/10.1182/asheducation-2009.1.701},\n\tdoi = {10.1182/asheducation-2009.1.701},\n\tabstract = {Advances in nanotechnology research have led to the creation of new generation of contrast agents, therapeutics, and delivery systems. These applications are expected to significantly improve the diagnosis and treatment of a variety of diseases. Two nanotechnologies—semiconductor and metallic nanostructures—are the most advanced in this young field and have been extensively investigated for clinical use. These nanostructures are currently the “model” for the developments of many novel nanostructures. This review describes their chemical design, tunable properties, and utility in medicine. Furthermore, we will describe the current understanding of their toxicity, which could be barriers to their use for human.},\n\tnumber = {1},\n\turldate = {2021-11-06},\n\tjournal = {Hematology},\n\tauthor = {Walkey, Carl and Sykes, Edward A. and Chan, Warren C. W.},\n\tmonth = jan,\n\tyear = {2009},\n\tpages = {701--707},\n\tfile = {Full Text PDF:files/2181/Walkey et al. - 2009 - Application of semiconductor and metal nanostructu.pdf:application/pdf;Snapshot:files/2182/Application-of-semiconductor-and-metal.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2022/01/Walkey-et-al.-2009-Application-of-semiconductor-and-metal-nanostructu.pdf}\n}\n\n
\n
\n\n\n
\n Advances in nanotechnology research have led to the creation of new generation of contrast agents, therapeutics, and delivery systems. These applications are expected to significantly improve the diagnosis and treatment of a variety of diseases. Two nanotechnologies—semiconductor and metallic nanostructures—are the most advanced in this young field and have been extensively investigated for clinical use. These nanostructures are currently the “model” for the developments of many novel nanostructures. This review describes their chemical design, tunable properties, and utility in medicine. Furthermore, we will describe the current understanding of their toxicity, which could be barriers to their use for human.\n
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\n  \n 2008\n \n \n (10)\n \n \n
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\n \n\n \n \n \n \n \n A Microrobotic Adherent Cell Injection System for Investigating Intracellular Behavior of Quantum Dots.\n \n \n \n\n\n \n Wang, W., Sun, Y., Zhang, M., Anderson, R., Langille, L., & Chan, W.\n\n\n \n\n\n\n In 2008 IEEE International Conference on Robotics and Automation, pages 407–412, May 2008. \n ISSN: 1050-4729\n\n\n\n
\n\n\n\n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
@inproceedings{wang_microrobotic_2008,\n\ttitle = {A {Microrobotic} {Adherent} {Cell} {Injection} {System} for {Investigating} {Intracellular} {Behavior} of {Quantum} {Dots}},\n\tdoi = {10.1109/ROBOT.2008.4543241},\n\tabstract = {This paper presents a semi-automated microrobotic system for adherent cell injection. Different from embryos/oocytes that have a spherical shape and regular morphology, adherent cells are flat with a thickness of a few micrometers and are highly irregular in morphology. Based on computer vision microscopy and motion control, the system coordinately controls a three-degrees-of-freedom microrobot and a precision XY stage. The microrobotic system demonstrates an injection speed of 25 endothelial cells per minute with a survival rate of 96\\% and a success rate of 82\\% (n=1012). The system has a high degree of performance consistency. It is immune to operator proficiency variations and from human fatigue, requiring a human operator to select injection destinations through computer mouse clicking as the only operator intervention. The microrobotic adherent cell injection system makes the injection of thousands of adherent cells practical and will enable our testing of intracellular behavior of semiconductive quantum dots (QDs).},\n\tbooktitle = {2008 {IEEE} {International} {Conference} on {Robotics} and {Automation}},\n\tauthor = {Wang, W.H. and Sun, Y. and Zhang, M. and Anderson, R. and Langille, L. and Chan, W.},\n\tmonth = may,\n\tyear = {2008},\n\tnote = {ISSN: 1050-4729},\n\tkeywords = {Adherent cell, Computer vision, Control systems, Embryo, endothelial cells, Humans, Immune system, microrobotic injection, Microscopy, molecule screening, Morphology, Motion control, quantum dots, Quantum dots, Shape},\n\tpages = {407--412},\n\tfile = {IEEE Xplore Full Text PDF:files/2166/Wang et al. - 2008 - A Microrobotic Adherent Cell Injection System for .pdf:application/pdf;IEEE Xplore Abstract Record:files/2170/4543241.html:text/html},\n}\n\n
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\n\n\n
\n This paper presents a semi-automated microrobotic system for adherent cell injection. Different from embryos/oocytes that have a spherical shape and regular morphology, adherent cells are flat with a thickness of a few micrometers and are highly irregular in morphology. Based on computer vision microscopy and motion control, the system coordinately controls a three-degrees-of-freedom microrobot and a precision XY stage. The microrobotic system demonstrates an injection speed of 25 endothelial cells per minute with a survival rate of 96% and a success rate of 82% (n=1012). The system has a high degree of performance consistency. It is immune to operator proficiency variations and from human fatigue, requiring a human operator to select injection destinations through computer mouse clicking as the only operator intervention. The microrobotic adherent cell injection system makes the injection of thousands of adherent cells practical and will enable our testing of intracellular behavior of semiconductive quantum dots (QDs).\n
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\n \n\n \n \n \n \n \n \n Facile and Rapid One-Step Mass Preparation of Quantum-Dot Barcodes.\n \n \n \n \n\n\n \n Fournier-Bidoz, S., Jennings, T. L., Klostranec, J. M., Fung, W., Rhee, A., Li, D., & Chan, W. C. W.\n\n\n \n\n\n\n Angewandte Chemie International Edition, 47(30): 5577–5581. 2008.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.200800409\n\n\n\n
\n\n\n\n \n \n \"FacilePaper\n  \n \n \n \"Facile paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
@article{fournier-bidoz_facile_2008,\n\ttitle = {Facile and {Rapid} {One}-{Step} {Mass} {Preparation} of {Quantum}-{Dot} {Barcodes}},\n\tvolume = {47},\n\tissn = {1521-3773},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/anie.200800409},\n\tdoi = {10.1002/anie.200800409},\n\tabstract = {Barcoding made easy: Quantum-dot-based barcodes were synthesized using a new concentration-controlled flow-focusing process. This one-step method yields robust barcodes that outperform current technologies and can be used in multiplexed detection of protein and genetic markers.},\n\tnumber = {30},\n\turldate = {2021-11-06},\n\tjournal = {Angewandte Chemie International Edition},\n\tauthor = {Fournier-Bidoz, Sébastien and Jennings, Travis L. and Klostranec, Jesse M. and Fung, Winnie and Rhee, Alex and Li, David and Chan, Warren C. W.},\n\tyear = {2008},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.200800409},\n\tkeywords = {barcodes, biosensors, fluorescence, multiplexing, quantum dots},\n\tpages = {5577--5581},\n\tfile = {Full Text PDF:files/2168/Fournier-Bidoz et al. - 2008 - Facile and Rapid One-Step Mass Preparation of Quan.pdf:application/pdf;Snapshot:files/2169/anie.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/anie.200800409.pdf}\n}\n\n
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\n Barcoding made easy: Quantum-dot-based barcodes were synthesized using a new concentration-controlled flow-focusing process. This one-step method yields robust barcodes that outperform current technologies and can be used in multiplexed detection of protein and genetic markers.\n
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\n \n\n \n \n \n \n \n \n Systematic Investigation of Preparing Biocompatible, Single, and Small ZnS-Capped CdSe Quantum Dots with Amphiphilic Polymers.\n \n \n \n \n\n\n \n Anderson, R. E., & Chan, W. C. W.\n\n\n \n\n\n\n ACS Nano, 2(7): 1341–1352. July 2008.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"SystematicPaper\n  \n \n \n \"Systematic paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{anderson_systematic_2008,\n\ttitle = {Systematic {Investigation} of {Preparing} {Biocompatible}, {Single}, and {Small} {ZnS}-{Capped} {CdSe} {Quantum} {Dots} with {Amphiphilic} {Polymers}},\n\tvolume = {2},\n\tissn = {1936-0851},\n\turl = {https://doi.org/10.1021/nn700450g},\n\tdoi = {10.1021/nn700450g},\n\tabstract = {The successful transfer of nanoparticles between solvents is critical for many applications. We evaluated the impact of amphiphilic polymer composition on the size, transfer efficiency, and biocompatibility of tri-n-octylphosphine oxide/hexadecylamine-stabilized semiconductor ZnS-capped CdSe and CdS-capped CdTexSe1−x quantum dots (QDs). We also investigated the adsorption of various proteins onto the surface of these QDs and studied the effect of surface chemistry on non-specific protein binding. The results from these studies will have implications in the design of QDs and other nanoparticles for biological and biomedical applications.},\n\tnumber = {7},\n\turldate = {2021-11-06},\n\tjournal = {ACS Nano},\n\tauthor = {Anderson, Robin E. and Chan, Warren C. W.},\n\tmonth = jul,\n\tyear = {2008},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {1341--1352},\n\tfile = {Full Text PDF:files/2172/Anderson and Chan - 2008 - Systematic Investigation of Preparing Biocompatibl.pdf:application/pdf;ACS Full Text Snapshot:files/2176/nn700450g.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nn700450g.pdf}\n}\n\n
\n
\n\n\n
\n The successful transfer of nanoparticles between solvents is critical for many applications. We evaluated the impact of amphiphilic polymer composition on the size, transfer efficiency, and biocompatibility of tri-n-octylphosphine oxide/hexadecylamine-stabilized semiconductor ZnS-capped CdSe and CdS-capped CdTexSe1−x quantum dots (QDs). We also investigated the adsorption of various proteins onto the surface of these QDs and studied the effect of surface chemistry on non-specific protein binding. The results from these studies will have implications in the design of QDs and other nanoparticles for biological and biomedical applications.\n
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\n \n\n \n \n \n \n \n \n Enhancing the Toxicity of Cancer Chemotherapeutics with Gold Nanorod Hyperthermia.\n \n \n \n \n\n\n \n Hauck, T. S., Jennings, T. L., Yatsenko, T., Kumaradas, J. C., & Chan, W. C. W.\n\n\n \n\n\n\n Advanced Materials, 20(20): 3832–3838. 2008.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.200800921\n\n\n\n
\n\n\n\n \n \n \"EnhancingPaper\n  \n \n \n \"Enhancing paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
@article{hauck_enhancing_2008,\n\ttitle = {Enhancing the {Toxicity} of {Cancer} {Chemotherapeutics} with {Gold} {Nanorod} {Hyperthermia}},\n\tvolume = {20},\n\tissn = {1521-4095},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/adma.200800921},\n\tdoi = {10.1002/adma.200800921},\n\tabstract = {The heat produced by optically excited gold nanorods is used to augment the chemotherapeutic agent cisplatin in killing tumor cells. This combined therapy kills 78\\% more cells than cisplatin alone, suggesting a synergistic interaction between these treatments.},\n\tnumber = {20},\n\turldate = {2021-11-06},\n\tjournal = {Advanced Materials},\n\tauthor = {Hauck, Tanya S. and Jennings, Travis L. and Yatsenko, Tetyana and Kumaradas, J. Carl and Chan, Warren C. W.},\n\tyear = {2008},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.200800921},\n\tkeywords = {Biomedical materials, Cells, Gold Nanorods, Nanotechnology, Optically active materials},\n\tpages = {3832--3838},\n\tfile = {Full Text PDF:files/2174/Hauck et al. - 2008 - Enhancing the Toxicity of Cancer Chemotherapeutics.pdf:application/pdf;Snapshot:files/2175/adma.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/adma.200800921.pdf}\n}\n\n
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\n The heat produced by optically excited gold nanorods is used to augment the chemotherapeutic agent cisplatin in killing tumor cells. This combined therapy kills 78% more cells than cisplatin alone, suggesting a synergistic interaction between these treatments.\n
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\n \n\n \n \n \n \n \n \n Biodegradable Quantum Dot Nanocomposites Enable Live Cell Labeling and Imaging of Cytoplasmic Targets.\n \n \n \n \n\n\n \n Kim, B. Y. S., Jiang, W., Oreopoulos, J., Yip, C. M., Rutka, J. T., & Chan, W. C. W.\n\n\n \n\n\n\n Nano Lett., 8(11): 3887–3892. November 2008.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"BiodegradablePaper\n  \n \n \n \"Biodegradable paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{kim_biodegradable_2008,\n\ttitle = {Biodegradable {Quantum} {Dot} {Nanocomposites} {Enable} {Live} {Cell} {Labeling} and {Imaging} of {Cytoplasmic} {Targets}},\n\tvolume = {8},\n\tissn = {1530-6984},\n\turl = {https://doi.org/10.1021/nl802311t},\n\tdoi = {10.1021/nl802311t},\n\tabstract = {Semiconductor quantum dots (QDs) offer great promise as the new generation of fluorescent probes to image and study biological processes. Despite their superior optical properties, QDs for live cell monitoring and tracking of cytoplasmic processes remain limited due to inefficient delivery methods available, altered state or function of cells during the delivery process and the requirement of surface-functionalized QDs for specific labeling of subcellular structures. Here, we present a noninvasive method to image subcellular structures in live cells using bioconjugated QD nanocomposites. By incorporating antibody-coated QDs within biodegradable polymeric nanospheres, we have designed a bioresponsive delivery system that undergoes endolysosomal to cytosolic translocation via pH-dependent reversal of nanocomposite surface charge polarity. Upon entering the cytosol, the polymer nanospheres undergo hydrolysis thus releasing the QD bioconjugates. This approach facilitates multiplexed labeling of subcellular structures inside live cells without the requirement of cell fixation or membrane permeabilization. As compared to conventional intracellular delivery techniques, this approach allows the high throughput cytoplasmic delivery of QDs with minimal toxicity to the cell. More importantly, this development demonstrates an important rational strategy for the design of a multifunctional nanosystem for biological applications.},\n\tnumber = {11},\n\turldate = {2021-11-06},\n\tjournal = {Nano Lett.},\n\tauthor = {Kim, Betty Y. S. and Jiang, Wen and Oreopoulos, John and Yip, Christopher M. and Rutka, James T. and Chan, Warren C. W.},\n\tmonth = nov,\n\tyear = {2008},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {3887--3892},\n\tfile = {Full Text PDF:files/2178/Kim et al. - 2008 - Biodegradable Quantum Dot Nanocomposites Enable Li.pdf:application/pdf;ACS Full Text Snapshot:files/2179/nl802311t.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nl802311t.pdf}\n}\n\n
\n
\n\n\n
\n Semiconductor quantum dots (QDs) offer great promise as the new generation of fluorescent probes to image and study biological processes. Despite their superior optical properties, QDs for live cell monitoring and tracking of cytoplasmic processes remain limited due to inefficient delivery methods available, altered state or function of cells during the delivery process and the requirement of surface-functionalized QDs for specific labeling of subcellular structures. Here, we present a noninvasive method to image subcellular structures in live cells using bioconjugated QD nanocomposites. By incorporating antibody-coated QDs within biodegradable polymeric nanospheres, we have designed a bioresponsive delivery system that undergoes endolysosomal to cytosolic translocation via pH-dependent reversal of nanocomposite surface charge polarity. Upon entering the cytosol, the polymer nanospheres undergo hydrolysis thus releasing the QD bioconjugates. This approach facilitates multiplexed labeling of subcellular structures inside live cells without the requirement of cell fixation or membrane permeabilization. As compared to conventional intracellular delivery techniques, this approach allows the high throughput cytoplasmic delivery of QDs with minimal toxicity to the cell. More importantly, this development demonstrates an important rational strategy for the design of a multifunctional nanosystem for biological applications.\n
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\n \n\n \n \n \n \n \n \n A system for high-speed microinjection of adherent cells.\n \n \n \n \n\n\n \n Wang, W., Sun, Y., Zhang, M., Anderson, R., Langille, L., & Chan, W.\n\n\n \n\n\n\n Review of Scientific Instruments, 79(10): 104302. October 2008.\n Publisher: American Institute of Physics\n\n\n\n
\n\n\n\n \n \n \"APaper\n  \n \n \n \"A paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{wang_system_2008,\n\ttitle = {A system for high-speed microinjection of adherent cells},\n\tvolume = {79},\n\tissn = {0034-6748},\n\turl = {http://aip.scitation.org/doi/full/10.1063/1.3006000},\n\tdoi = {10.1063/1.3006000},\n\tabstract = {This paper reports on a semi-automated microrobotic system for adherent cell injection. Different from embryos/oocytes that have a spherical shape and regular morphology, adherent cells are flat with a thickness of a few micrometers and are highly irregular in morphology. Based on computer vision microscopy and motion control, the system coordinately controls a three-degrees-of-freedom microrobot and a precision \n𝑋𝑌\nXY\n stage, demonstrating an injection speed of 25 endothelial cells per minute with a survival rate of 95.7\\% and a success rate of 82.4\\% \n(𝑛=1012)\n(n=1012)\n. The system has a high degree of performance consistency. It is operator skill independent and immune from human fatigue, only requiring a human operator to select injection destinations through computer mouse clicking as the only operator intervention. The microrobotic system makes the injection of a large number of adherent cells practical for testing cellular responses to foreign molecules.},\n\tnumber = {10},\n\turldate = {2021-11-06},\n\tjournal = {Review of Scientific Instruments},\n\tauthor = {Wang, Wenhui and Sun, Yu and Zhang, Ming and Anderson, Robin and Langille, Lowell and Chan, Warren},\n\tmonth = oct,\n\tyear = {2008},\n\tnote = {Publisher: American Institute of Physics},\n\tpages = {104302},\n\tfile = {Full Text PDF:files/2184/Wang et al. - 2008 - A system for high-speed microinjection of adherent.pdf:application/pdf},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/1.3006000.pdf}\n}\n\n
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\n This paper reports on a semi-automated microrobotic system for adherent cell injection. Different from embryos/oocytes that have a spherical shape and regular morphology, adherent cells are flat with a thickness of a few micrometers and are highly irregular in morphology. Based on computer vision microscopy and motion control, the system coordinately controls a three-degrees-of-freedom microrobot and a precision 𝑋𝑌 XY stage, demonstrating an injection speed of 25 endothelial cells per minute with a survival rate of 95.7% and a success rate of 82.4% (𝑛=1012) (n=1012) . The system has a high degree of performance consistency. It is operator skill independent and immune from human fatigue, only requiring a human operator to select injection destinations through computer mouse clicking as the only operator intervention. The microrobotic system makes the injection of a large number of adherent cells practical for testing cellular responses to foreign molecules.\n
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\n \n\n \n \n \n \n \n \n Effects of Microbead Surface Chemistry on DNA Loading and Hybridization Efficiency.\n \n \n \n \n\n\n \n Jennings, T. L., Rahman, K. S., Fournier-Bidoz, S., & Chan, W. C. W.\n\n\n \n\n\n\n Anal. Chem., 80(8): 2849–2856. April 2008.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"EffectsPaper\n  \n \n \n \"Effects paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{jennings_effects_2008,\n\ttitle = {Effects of {Microbead} {Surface} {Chemistry} on {DNA} {Loading} and {Hybridization} {Efficiency}},\n\tvolume = {80},\n\tissn = {0003-2700},\n\turl = {https://doi.org/10.1021/ac7026035},\n\tdoi = {10.1021/ac7026035},\n\tabstract = {Polymer microbeads are witnessing renewed interest for performing biomolecule recognition assays with distinct advantages over planar microarray technology. In this study, DNA hybridization assays are performed on the surfaces of 1-μm-diameter, synthetically modified polystyrene microbeads. The microbead surfaces contain varying amounts of poly(acrylic acid) as a source of carboxylate groups to which a DNA capture strand may bind. Through a series of controlled experiments in which the microbead carboxylate density and DNA:surface area ratios are systematically altered, we find that the density of carboxylate groups on the microbead surface may be the most important parameter affecting not only the total number of DNA strands that may bind to the microbead surface but, surprisingly, also the efficiency of DNA hybridization with complementary strands. These studies are aimed directly at understanding the physical interactions between DNA strands and an anionic microbead surface.},\n\tnumber = {8},\n\turldate = {2021-11-06},\n\tjournal = {Anal. Chem.},\n\tauthor = {Jennings, T. L. and Rahman, K. S. and Fournier-Bidoz, S. and Chan, W. C. W.},\n\tmonth = apr,\n\tyear = {2008},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {2849--2856},\n\tfile = {Full Text PDF:files/2198/Jennings et al. - 2008 - Effects of Microbead Surface Chemistry on DNA Load.pdf:application/pdf;ACS Full Text Snapshot:files/2204/ac7026035.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/ac7026035.pdf}\n}\n\n
\n
\n\n\n
\n Polymer microbeads are witnessing renewed interest for performing biomolecule recognition assays with distinct advantages over planar microarray technology. In this study, DNA hybridization assays are performed on the surfaces of 1-μm-diameter, synthetically modified polystyrene microbeads. The microbead surfaces contain varying amounts of poly(acrylic acid) as a source of carboxylate groups to which a DNA capture strand may bind. Through a series of controlled experiments in which the microbead carboxylate density and DNA:surface area ratios are systematically altered, we find that the density of carboxylate groups on the microbead surface may be the most important parameter affecting not only the total number of DNA strands that may bind to the microbead surface but, surprisingly, also the efficiency of DNA hybridization with complementary strands. These studies are aimed directly at understanding the physical interactions between DNA strands and an anionic microbead surface.\n
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\n \n\n \n \n \n \n \n \n Nanoparticle-mediated cellular response is size-dependent.\n \n \n \n \n\n\n \n Jiang, W., Kim, B. Y. S., Rutka, J. T., & Chan, W. C. W.\n\n\n \n\n\n\n Nature Nanotech, 3(3): 145–150. March 2008.\n Bandiera_abtest: a Cg_type: Nature Research Journals Number: 3 Primary_atype: Research Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n \"Nanoparticle-mediatedPaper\n  \n \n \n \"Nanoparticle-mediated paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
@article{jiang_nanoparticle-mediated_2008,\n\ttitle = {Nanoparticle-mediated cellular response is size-dependent},\n\tvolume = {3},\n\tcopyright = {2008 Nature Publishing Group},\n\tissn = {1748-3395},\n\turl = {https://www.nature.com/articles/nnano.2008.30},\n\tdoi = {10.1038/nnano.2008.30},\n\tabstract = {Nanostructures of different sizes, shapes and material properties have many applications in biomedical imaging, clinical diagnostics and therapeutics1,2,3,4,5,6. In spite of what has been achieved so far, a complete understanding of how cells interact with nanostructures of well-defined sizes, at the molecular level, remains poorly understood. Here we show that gold and silver nanoparticles coated with antibodies can regulate the process of membrane receptor internalization. The binding and activation of membrane receptors and subsequent protein expression strongly depend on nanoparticle size. Although all nanoparticles within the 2–100 nm size range were found to alter signalling processes essential for basic cell functions (including cell death)7, 40- and 50-nm nanoparticles demonstrated the greatest effect. These results show that nanoparticles should no longer be viewed as simple carriers for biomedical applications, but can also play an active role in mediating biological effects. The findings presented here may assist in the design of nanoscale delivery and therapeutic systems and provide insights into nanotoxicity.},\n\tlanguage = {en},\n\tnumber = {3},\n\turldate = {2021-11-06},\n\tjournal = {Nature Nanotech},\n\tauthor = {Jiang, Wen and Kim, Betty Y. S. and Rutka, James T. and Chan, Warren C. W.},\n\tmonth = mar,\n\tyear = {2008},\n\tnote = {Bandiera\\_abtest: a\nCg\\_type: Nature Research Journals\nNumber: 3\nPrimary\\_atype: Research\nPublisher: Nature Publishing Group},\n\tkeywords = {general, Materials Science, Nanotechnology, Nanotechnology and Microengineering},\n\tpages = {145--150},\n\tfile = {Full Text PDF:files/2200/Jiang et al. - 2008 - Nanoparticle-mediated cellular response is size-de.pdf:application/pdf;Snapshot:files/2202/nnano.2008.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nnano.2008.30.pdf}\n}\n\n
\n
\n\n\n
\n Nanostructures of different sizes, shapes and material properties have many applications in biomedical imaging, clinical diagnostics and therapeutics1,2,3,4,5,6. In spite of what has been achieved so far, a complete understanding of how cells interact with nanostructures of well-defined sizes, at the molecular level, remains poorly understood. Here we show that gold and silver nanoparticles coated with antibodies can regulate the process of membrane receptor internalization. The binding and activation of membrane receptors and subsequent protein expression strongly depend on nanoparticle size. Although all nanoparticles within the 2–100 nm size range were found to alter signalling processes essential for basic cell functions (including cell death)7, 40- and 50-nm nanoparticles demonstrated the greatest effect. These results show that nanoparticles should no longer be viewed as simple carriers for biomedical applications, but can also play an active role in mediating biological effects. The findings presented here may assist in the design of nanoscale delivery and therapeutic systems and provide insights into nanotoxicity.\n
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\n \n\n \n \n \n \n \n \n Assessing Near-Infrared Quantum Dots for Deep Tissue, Organ, and Animal Imaging Applications.\n \n \n \n \n\n\n \n Jiang, W., Singhal, A., Kim, B. Y., Zheng, J., Rutka, J. T., Wang, C., & Chan, W. C.\n\n\n \n\n\n\n JALA: Journal of the Association for Laboratory Automation, 13(1): 6–12. February 2008.\n Publisher: SAGE Publications Inc\n\n\n\n
\n\n\n\n \n \n \"AssessingPaper\n  \n \n \n \"Assessing paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{jiang_assessing_2008,\n\ttitle = {Assessing {Near}-{Infrared} {Quantum} {Dots} for {Deep} {Tissue}, {Organ}, and {Animal} {Imaging} {Applications}},\n\tvolume = {13},\n\tissn = {1535-5535},\n\turl = {https://doi.org/10.1016/j.jala.2007.09.002},\n\tdoi = {10.1016/j.jala.2007.09.002},\n\tabstract = {Semiconductor quantum dots (Qdots) have emerged as novel ultrasensitive optical probes to target, detect, and image fundamental events occurring within the biological system. In particular, near-infrared (near-IR) Qdots holds great promise as in vivo contrast agents for real-time bioimaging capabilities. In this study, biocompatible near-IR Qdots are used to image organs, tissues, and cells. Compared to visible Qdots, we obtained a significant enhancement in signal detection sensitivity for imaging deep tissues and organs. In addition, biomolecules were used to target these optical contrast agents for multiplexed imaging of cells and organs in vivo. The ability to simultaneously distinguish emission profiles of multiple near-IR Qdots will likely emerge as important tools for addressing fundamental questions in molecular biology and in medical sciences.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2021-11-06},\n\tjournal = {JALA: Journal of the Association for Laboratory Automation},\n\tauthor = {Jiang, Wen and Singhal, Anupam and Kim, Betty Y.S. and Zheng, Jianing and Rutka, James T. and Wang, Chen and Chan, Warren C.W.},\n\tmonth = feb,\n\tyear = {2008},\n\tnote = {Publisher: SAGE Publications Inc},\n\tkeywords = {animal, in vivo imaging, multiplexed imaging, near-infrared imaging, optical imaging, organ, quantum dots, targeting},\n\tpages = {6--12},\n\tfile = {SAGE PDF Full Text:files/2205/Jiang et al. - 2008 - Assessing Near-Infrared Quantum Dots for Deep Tiss.pdf:application/pdf},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/j.jala_.2007.09.002.pdf}\n}\n\n
\n
\n\n\n
\n Semiconductor quantum dots (Qdots) have emerged as novel ultrasensitive optical probes to target, detect, and image fundamental events occurring within the biological system. In particular, near-infrared (near-IR) Qdots holds great promise as in vivo contrast agents for real-time bioimaging capabilities. In this study, biocompatible near-IR Qdots are used to image organs, tissues, and cells. Compared to visible Qdots, we obtained a significant enhancement in signal detection sensitivity for imaging deep tissues and organs. In addition, biomolecules were used to target these optical contrast agents for multiplexed imaging of cells and organs in vivo. The ability to simultaneously distinguish emission profiles of multiple near-IR Qdots will likely emerge as important tools for addressing fundamental questions in molecular biology and in medical sciences.\n
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\n \n\n \n \n \n \n \n \n Assessing the Effect of Surface Chemistry on Gold Nanorod Uptake, Toxicity, and Gene Expression in Mammalian Cells.\n \n \n \n \n\n\n \n Hauck, T. S., Ghazani, A. A., & Chan, W. C. W.\n\n\n \n\n\n\n Small, 4(1): 153–159. 2008.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/smll.200700217\n\n\n\n
\n\n\n\n \n \n \"AssessingPaper\n  \n \n \n \"Assessing paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
@article{hauck_assessing_2008,\n\ttitle = {Assessing the {Effect} of {Surface} {Chemistry} on {Gold} {Nanorod} {Uptake}, {Toxicity}, and {Gene} {Expression} in {Mammalian} {Cells}},\n\tvolume = {4},\n\tissn = {1613-6829},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/smll.200700217},\n\tdoi = {10.1002/smll.200700217},\n\tabstract = {Through the use of various layer-by-layer polyelectrolyte (PE) coating schemes, such as the common poly(diallyldimethylammonium chloride)–poly(4-styrenesulfonic acid) (PDADMAC-PSS) system, the mammalian cellular uptake of gold nanorods can be tuned from very high to very low by manipulating the surface charge and functional groups of the PEs. The toxicity of these nanorods is also examined. Since the PE coatings are individually toxic, the toxicity of nanorods coated in these PEs is measured and cells are found to be greater than 90\\% viable in nearly all cases, even at very high concentrations. This viability assay may not be a complete indicator of toxicity, and thus gene-expression analysis is used to examine the molecular changes of cells exposed to PDADMAC-coated nanorods, which enter cells at the highest concentrations. Indicators of cell stress, such as heat-shock proteins, are not significantly up- or down-regulated following nanorod uptake, which suggests that PDADMAC-coated gold nanorods have negligible impact on cell function. Furthermore, a very low number of genes experience any significant change in expression (0.35\\% of genes examined). These results indicate that gold nanorods are well suited for therapeutic applications, such as thermal cancer therapy, due to their tunable cell uptake and low toxicity.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2021-11-06},\n\tjournal = {Small},\n\tauthor = {Hauck, Tanya S. and Ghazani, Arezou A. and Chan, Warren C. W.},\n\tyear = {2008},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/smll.200700217},\n\tkeywords = {gene expression, gold, layered materials, nanorods, polyelectrolytes},\n\tpages = {153--159},\n\tfile = {Full Text PDF:files/2207/Hauck et al. - 2008 - Assessing the Effect of Surface Chemistry on Gold .pdf:application/pdf;Snapshot:files/2209/smll.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/smll.200700217.pdf}\n}\n\n
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\n Through the use of various layer-by-layer polyelectrolyte (PE) coating schemes, such as the common poly(diallyldimethylammonium chloride)–poly(4-styrenesulfonic acid) (PDADMAC-PSS) system, the mammalian cellular uptake of gold nanorods can be tuned from very high to very low by manipulating the surface charge and functional groups of the PEs. The toxicity of these nanorods is also examined. Since the PE coatings are individually toxic, the toxicity of nanorods coated in these PEs is measured and cells are found to be greater than 90% viable in nearly all cases, even at very high concentrations. This viability assay may not be a complete indicator of toxicity, and thus gene-expression analysis is used to examine the molecular changes of cells exposed to PDADMAC-coated nanorods, which enter cells at the highest concentrations. Indicators of cell stress, such as heat-shock proteins, are not significantly up- or down-regulated following nanorod uptake, which suggests that PDADMAC-coated gold nanorods have negligible impact on cell function. Furthermore, a very low number of genes experience any significant change in expression (0.35% of genes examined). These results indicate that gold nanorods are well suited for therapeutic applications, such as thermal cancer therapy, due to their tunable cell uptake and low toxicity.\n
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\n  \n 2007\n \n \n (10)\n \n \n
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\n \n\n \n \n \n \n \n \n Elucidating the Mechanism of Cellular Uptake and Removal of Protein-Coated Gold Nanoparticles of Different Sizes and Shapes.\n \n \n \n \n\n\n \n Chithrani, B. D., & Chan, W. C. W.\n\n\n \n\n\n\n Nano Lett., 7(6): 1542–1550. June 2007.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"ElucidatingPaper\n  \n \n \n \"Elucidating paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{chithrani_elucidating_2007,\n\ttitle = {Elucidating the {Mechanism} of {Cellular} {Uptake} and {Removal} of {Protein}-{Coated} {Gold} {Nanoparticles} of {Different} {Sizes} and {Shapes}},\n\tvolume = {7},\n\tissn = {1530-6984},\n\turl = {https://doi.org/10.1021/nl070363y},\n\tdoi = {10.1021/nl070363y},\n\tabstract = {We investigated the mechanism by which transferrin-coated gold nanoparticles (Au NP) of different sizes and shapes entered mammalian cells. We determined that transferrin-coated Au NP entered the cells via clathrin-mediated endocytosis pathway. The NPs exocytosed out of the cells in a linear relationship to size. This was different than the relationship between uptake and size. Furthermore, we developed a mathematical equation to predict the relationship of size versus exocytosis for different cell lines. These studies will provide guidelines for developing NPs for imaging and drug delivery applications, which will require “controlling” NP accumulation rate. These studies will also have implications in determining nanotoxicity.},\n\tnumber = {6},\n\turldate = {2021-11-06},\n\tjournal = {Nano Lett.},\n\tauthor = {Chithrani, B. Devika and Chan, Warren C. W.},\n\tmonth = jun,\n\tyear = {2007},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {1542--1550},\n\tfile = {Full Text PDF:files/2186/Chithrani and Chan - 2007 - Elucidating the Mechanism of Cellular Uptake and R.pdf:application/pdf;ACS Full Text Snapshot:files/2189/nl070363y.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nl070363y.pdf}\n}\n\n
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\n We investigated the mechanism by which transferrin-coated gold nanoparticles (Au NP) of different sizes and shapes entered mammalian cells. We determined that transferrin-coated Au NP entered the cells via clathrin-mediated endocytosis pathway. The NPs exocytosed out of the cells in a linear relationship to size. This was different than the relationship between uptake and size. Furthermore, we developed a mathematical equation to predict the relationship of size versus exocytosis for different cell lines. These studies will provide guidelines for developing NPs for imaging and drug delivery applications, which will require “controlling” NP accumulation rate. These studies will also have implications in determining nanotoxicity.\n
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\n \n\n \n \n \n \n \n \n High throughput quantification of cancer antigens of tumor biopsies: A novel strategy using quantum dot nanocrystals.\n \n \n \n \n\n\n \n Ghazani, A., Aviel-Ronen1, S., Lee, J. A., Klostranec, J., Xiang, Q., Chan, W., & Tsao, M.\n\n\n \n\n\n\n Cancer Res, 67(9 Supplement): 183–183. May 2007.\n Publisher: American Association for Cancer Research Section: Clinical Research\n\n\n\n
\n\n\n\n \n \n \"HighPaper\n  \n \n\n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{ghazani_high_2007,\n\ttitle = {High throughput quantification of cancer antigens of tumor biopsies: {A} novel strategy using quantum dot nanocrystals},\n\tvolume = {67},\n\tcopyright = {American Association for Cancer Research},\n\tissn = {0008-5472, 1538-7445},\n\tshorttitle = {High throughput quantification of cancer antigens of tumor biopsies},\n\turl = {https://cancerres.aacrjournals.org/content/67/9_Supplement/183},\n\tabstract = {183\nCurrent analysis of tumor progression and staging of tumor biopsies include microscopic examination of hundreds of tissue samples and evaluation of protein expression levels. The intensity of cancer markers, as determined by visual analysis of colorimetric stains, is used to define a numerical score for staging of tumor biopsies and provide merely semi quantitative valuesand a limited range especially at a very low or high expression level. Conventional fluorescence dyes have also limited applications, as the accuracy of quantification can be compromised by the photo-bleaching property of fluorophores. This study aimed to develop a method for quantifications of tumor antigens in an accurate, sensitive and effective manner. We employed quantum dots (QDs), semiconductor nanocrystals, as immulabeling agents. QDs have many advantageous properties over traditional fluorescent dyes including emitting significantly brighter signals over tissue autofluorescent, being resistant to photobleaching and enabling simultaneous detection of multiplex biomarkers. Using QD nanocrystals in conjunction with optical spectroscopy, commonly used for single molecule fluorescence analysis, we have developed a method to quantify protein expression in tissue microarray. We have also developed a set of automated algorithms to remove tissue autofluorescence and perform a comprehensive analysis of protein expression data. Validation studies were carried out using epidermal growth factor receptor (EGFR) on 8 different lung carcinoma xenografts, known to have differential expression level of EGFR. Data obtained from this method were shown to be congruent to endogenous mRNA level of EGFR obtained from Quantitative Real Time Polymerase Chain Reaction (Q-RT-PCR). To validate this method in primary tumor samples, we compared the measurements obtained from QD-immunolabeling against EGFR for the tumor regions assessed to the subjective immunohistochemistry scoring on non-small cell lung cancer in a tissue microarray slide. We found a strong correlation of 96\\% between the two methods. Application of QD-based immunolabeling and quantification method in molecular pathology enables accurate, sensitive and effective quantitative analysis of protein expression in tumor tissues, with potential impact on cancer diagnosis and treatment.},\n\tlanguage = {en},\n\tnumber = {9 Supplement},\n\turldate = {2021-11-06},\n\tjournal = {Cancer Res},\n\tauthor = {Ghazani, Arezou and Aviel-Ronen1, Sarit and Lee, Jeongjin A. and Klostranec, Jesse and Xiang, Qing and Chan, Warren and Tsao, Ming},\n\tmonth = may,\n\tyear = {2007},\n\tnote = {Publisher: American Association for Cancer Research\nSection: Clinical Research},\n\tpages = {183--183},\n\tfile = {Snapshot:files/2191/183.html:text/html},\n}\n\n
\n
\n\n\n
\n 183 Current analysis of tumor progression and staging of tumor biopsies include microscopic examination of hundreds of tissue samples and evaluation of protein expression levels. The intensity of cancer markers, as determined by visual analysis of colorimetric stains, is used to define a numerical score for staging of tumor biopsies and provide merely semi quantitative valuesand a limited range especially at a very low or high expression level. Conventional fluorescence dyes have also limited applications, as the accuracy of quantification can be compromised by the photo-bleaching property of fluorophores. This study aimed to develop a method for quantifications of tumor antigens in an accurate, sensitive and effective manner. We employed quantum dots (QDs), semiconductor nanocrystals, as immulabeling agents. QDs have many advantageous properties over traditional fluorescent dyes including emitting significantly brighter signals over tissue autofluorescent, being resistant to photobleaching and enabling simultaneous detection of multiplex biomarkers. Using QD nanocrystals in conjunction with optical spectroscopy, commonly used for single molecule fluorescence analysis, we have developed a method to quantify protein expression in tissue microarray. We have also developed a set of automated algorithms to remove tissue autofluorescence and perform a comprehensive analysis of protein expression data. Validation studies were carried out using epidermal growth factor receptor (EGFR) on 8 different lung carcinoma xenografts, known to have differential expression level of EGFR. Data obtained from this method were shown to be congruent to endogenous mRNA level of EGFR obtained from Quantitative Real Time Polymerase Chain Reaction (Q-RT-PCR). To validate this method in primary tumor samples, we compared the measurements obtained from QD-immunolabeling against EGFR for the tumor regions assessed to the subjective immunohistochemistry scoring on non-small cell lung cancer in a tissue microarray slide. We found a strong correlation of 96% between the two methods. Application of QD-based immunolabeling and quantification method in molecular pathology enables accurate, sensitive and effective quantitative analysis of protein expression in tumor tissues, with potential impact on cancer diagnosis and treatment.\n
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\n \n\n \n \n \n \n \n \n Convergence of Quantum Dot Barcodes with Microfluidics and Signal Processing for Multiplexed High-Throughput Infectious Disease Diagnostics.\n \n \n \n \n\n\n \n Klostranec, J. M., Xiang, Q., Farcas, G. A., Lee, J. A., Rhee, A., Lafferty, E. I., Perrault, S. D., Kain, K. C., & Chan, W. C. W.\n\n\n \n\n\n\n Nano Lett., 7(9): 2812–2818. September 2007.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"ConvergencePaper\n  \n \n \n \"Convergence paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{klostranec_convergence_2007,\n\ttitle = {Convergence of {Quantum} {Dot} {Barcodes} with {Microfluidics} and {Signal} {Processing} for {Multiplexed} {High}-{Throughput} {Infectious} {Disease} {Diagnostics}},\n\tvolume = {7},\n\tissn = {1530-6984},\n\turl = {https://doi.org/10.1021/nl071415m},\n\tdoi = {10.1021/nl071415m},\n\tabstract = {Through the convergence of nano- and microtechnologies (quantum dots and microfluidics), we have created a diagnostic system capable of multiplexed, high-throughput analysis of infectious agents in human serum samples. We demonstrate, as a proof-of-concept, the ability to detect serum biomarkers of the most globally prevalent blood-borne infectious diseases (i.e., hepatitis B, hepatitis C, and HIV) with low sample volume ({\\textless}100 μL), rapidity ({\\textless}1 h), and 50 times greater sensitivity than that of currently available FDA-approved methods. We further show precision for detecting multiple biomarkers simultaneously in serum with minimal cross-reactivity. This device could be further developed into a portable handheld point-of-care diagnostic system, which would represent a major advance in detecting, monitoring, treating, and preventing infectious disease spread in the developed and developing worlds.},\n\tnumber = {9},\n\turldate = {2021-11-06},\n\tjournal = {Nano Lett.},\n\tauthor = {Klostranec, Jesse M. and Xiang, Qing and Farcas, Gabriella A. and Lee, Jeongjin A. and Rhee, Alex and Lafferty, Erin I. and Perrault, Steven D. and Kain, Kevin C. and Chan, Warren C. W.},\n\tmonth = sep,\n\tyear = {2007},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {2812--2818},\n\tfile = {Full Text PDF:files/2190/Klostranec et al. - 2007 - Convergence of Quantum Dot Barcodes with Microflui.pdf:application/pdf;ACS Full Text Snapshot:files/2192/nl071415m.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nl071415m.pdf}\n}\n\n
\n
\n\n\n
\n Through the convergence of nano- and microtechnologies (quantum dots and microfluidics), we have created a diagnostic system capable of multiplexed, high-throughput analysis of infectious agents in human serum samples. We demonstrate, as a proof-of-concept, the ability to detect serum biomarkers of the most globally prevalent blood-borne infectious diseases (i.e., hepatitis B, hepatitis C, and HIV) with low sample volume (\\textless100 μL), rapidity (\\textless1 h), and 50 times greater sensitivity than that of currently available FDA-approved methods. We further show precision for detecting multiple biomarkers simultaneously in serum with minimal cross-reactivity. This device could be further developed into a portable handheld point-of-care diagnostic system, which would represent a major advance in detecting, monitoring, treating, and preventing infectious disease spread in the developed and developing worlds.\n
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\n \n\n \n \n \n \n \n \n Gold nanoshells in cancer imaging and therapy: towards clinical application.\n \n \n \n \n\n\n \n Hauck, T. S, & Chan, W. C.\n\n\n \n\n\n\n Nanomedicine, 2(5): 735–738. October 2007.\n Publisher: Future Medicine\n\n\n\n
\n\n\n\n \n \n \"GoldPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{hauck_gold_2007,\n\ttitle = {Gold nanoshells in cancer imaging and therapy: towards clinical application},\n\tvolume = {2},\n\tissn = {1743-5889},\n\tshorttitle = {Gold nanoshells in cancer imaging and therapy},\n\turl = {https://www.futuremedicine.com/doi/10.2217/17435889.2.5.735},\n\tdoi = {10.2217/17435889.2.5.735},\n\tabstract = {Evaluation of: Gobin AM, Lee MH, Halas NJ, James WD, Drezek RA, West JL: Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy. Nano Lett. 7, 1929–1934 (2007)[1]. Although hyperthermia has been a promising method of cancer treatment for decades, traditional means of heating tissues involve invasive catheters or whole-body heating systems. The use of nanoparticles in hyperthermia therapy has been developed over the last 4 years and involves the near-infrared heating of these nanoshells without harming healthy tissues. The paper under evaluation demonstrates the improved optical imaging of tumors with nanoshells and the improved long-term survival of mice treated with these particles and near-infrared irradiation. The implications of this work and important future steps are explored in this evaluation.},\n\tnumber = {5},\n\turldate = {2021-11-06},\n\tjournal = {Nanomedicine},\n\tauthor = {Hauck, Tanya S and Chan, Warren CW},\n\tmonth = oct,\n\tyear = {2007},\n\tnote = {Publisher: Future Medicine},\n\tpages = {735--738},\n\tfile = {Hauck and Chan - 2007 - Gold nanoshells in cancer imaging and therapy tow.pdf:files/2196/Hauck and Chan - 2007 - Gold nanoshells in cancer imaging and therapy tow.pdf:application/pdf},\n}\n\n
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\n\n\n
\n Evaluation of: Gobin AM, Lee MH, Halas NJ, James WD, Drezek RA, West JL: Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy. Nano Lett. 7, 1929–1934 (2007)[1]. Although hyperthermia has been a promising method of cancer treatment for decades, traditional means of heating tissues involve invasive catheters or whole-body heating systems. The use of nanoparticles in hyperthermia therapy has been developed over the last 4 years and involves the near-infrared heating of these nanoshells without harming healthy tissues. The paper under evaluation demonstrates the improved optical imaging of tumors with nanoshells and the improved long-term survival of mice treated with these particles and near-infrared irradiation. The implications of this work and important future steps are explored in this evaluation.\n
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\n \n\n \n \n \n \n \n \n Nanotoxicity: the growing need for in vivo study.\n \n \n \n \n\n\n \n Fischer, H. C, & Chan, W. C.\n\n\n \n\n\n\n Current Opinion in Biotechnology, 18(6): 565–571. December 2007.\n \n\n\n\n
\n\n\n\n \n \n \"Nanotoxicity:Paper\n  \n \n \n \"Nanotoxicity: paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{fischer_nanotoxicity_2007,\n\tseries = {Chemical biotechnology / {Pharmaceutical} biotechnology},\n\ttitle = {Nanotoxicity: the growing need for in vivo study},\n\tvolume = {18},\n\tissn = {0958-1669},\n\tshorttitle = {Nanotoxicity},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0958166907001553},\n\tdoi = {10.1016/j.copbio.2007.11.008},\n\tabstract = {Nanotoxicology is emerging as an important subdiscipline of nanotechnology. Nanotoxicology refers to the study of the interactions of nanostructures with biological systems with an emphasis on elucidating the relationship between the physical and chemical properties (e.g. size, shape, surface chemistry, composition, and aggregation) of nanostructures with induction of toxic biological responses. In the past five years, a majority of nanotoxicity research has focused on cell culture systems; however, the data from these studies could be misleading and will require verification from animal experiments. In vivo systems are extremely complicated and the interactions of the nanostructures with biological components, such as proteins and cells, could lead to unique biodistribution, clearance, immune response, and metabolism. An understanding of the relationship between the physical and chemical properties of the nanostructure and their in vivo behavior would provide a basis for assessing toxic response and more importantly could lead to predictive models for assessing toxicity. In this review article, we describe the assumptions and challenges in the nanotoxicity field and provide a rationale for in vivo animal studies to assess nanotoxicity.},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2021-11-06},\n\tjournal = {Current Opinion in Biotechnology},\n\tauthor = {Fischer, Hans C and Chan, Warren CW},\n\tmonth = dec,\n\tyear = {2007},\n\tpages = {565--571},\n\tfile = {ScienceDirect Full Text PDF:files/2208/Fischer and Chan - 2007 - Nanotoxicity the growing need for in vivo study.pdf:application/pdf},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/1-s2.0-S0958166907001553-main.pdf}\n}\n\n
\n
\n\n\n
\n Nanotoxicology is emerging as an important subdiscipline of nanotechnology. Nanotoxicology refers to the study of the interactions of nanostructures with biological systems with an emphasis on elucidating the relationship between the physical and chemical properties (e.g. size, shape, surface chemistry, composition, and aggregation) of nanostructures with induction of toxic biological responses. In the past five years, a majority of nanotoxicity research has focused on cell culture systems; however, the data from these studies could be misleading and will require verification from animal experiments. In vivo systems are extremely complicated and the interactions of the nanostructures with biological components, such as proteins and cells, could lead to unique biodistribution, clearance, immune response, and metabolism. An understanding of the relationship between the physical and chemical properties of the nanostructure and their in vivo behavior would provide a basis for assessing toxic response and more importantly could lead to predictive models for assessing toxicity. In this review article, we describe the assumptions and challenges in the nanotoxicity field and provide a rationale for in vivo animal studies to assess nanotoxicity.\n
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\n \n\n \n \n \n \n \n \n Toward the Accurate Read-out of Quantum Dot Barcodes: Design of Deconvolution Algorithms and Assessment of Fluorescence Signals in Buffer.\n \n \n \n \n\n\n \n Lee, J. A., Hung, A., Mardyani, S., Rhee, A., Klostranec, J., Mu, Y., Li, D., & Chan, W. C. W.\n\n\n \n\n\n\n Advanced Materials, 19(20): 3113–3118. 2007.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.200701955\n\n\n\n
\n\n\n\n \n \n \"TowardPaper\n  \n \n \n \"Toward paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n\n\n\n
\n
@article{lee_toward_2007,\n\ttitle = {Toward the {Accurate} {Read}-out of {Quantum} {Dot} {Barcodes}: {Design} of {Deconvolution} {Algorithms} and {Assessment} of {Fluorescence} {Signals} in {Buffer}},\n\tvolume = {19},\n\tissn = {1521-4095},\n\tshorttitle = {Toward the {Accurate} {Read}-out of {Quantum} {Dot} {Barcodes}},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/adma.200701955},\n\tdoi = {10.1002/adma.200701955},\n\tabstract = {Signal processing methods and constraints for discerning the fluorescence signals of the QD-barcodes are explored. QD-barcodes and their corresponding fluorescence spectra (see figure) require signal processing algorithms in order to be uniquely identified. Using these algorithms, we determined the number of available barcodes for use in biological detection. We also studied the impact of chemical constraints such as buffer and pH level on the barcode and read-out design.},\n\tnumber = {20},\n\turldate = {2021-11-06},\n\tjournal = {Advanced Materials},\n\tauthor = {Lee, J. A. and Hung, A. and Mardyani, S. and Rhee, A. and Klostranec, J. and Mu, Y. and Li, D. and Chan, W. C. W.},\n\tyear = {2007},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.200701955},\n\tkeywords = {Biocompatible materials, Quantum dots, Sensors},\n\tpages = {3113--3118},\n\tfile = {Full Text PDF:files/2211/Lee et al. - 2007 - Toward the Accurate Read-out of Quantum Dot Barcod.pdf:application/pdf;Snapshot:files/2212/adma.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/adma.200701955.pdf}\n}\n\n
\n
\n\n\n
\n Signal processing methods and constraints for discerning the fluorescence signals of the QD-barcodes are explored. QD-barcodes and their corresponding fluorescence spectra (see figure) require signal processing algorithms in order to be uniquely identified. Using these algorithms, we determined the number of available barcodes for use in biological detection. We also studied the impact of chemical constraints such as buffer and pH level on the barcode and read-out design.\n
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\n \n\n \n \n \n \n \n \n Advances and challenges of nanotechnology-based drug delivery systems.\n \n \n \n \n\n\n \n Jiang, W., Kim, B. Y., Rutka, J. T, & Chan, W. C.\n\n\n \n\n\n\n Expert Opinion on Drug Delivery, 4(6): 621–633. November 2007.\n Publisher: Taylor & Francis _eprint: https://doi.org/10.1517/17425247.4.6.621\n\n\n\n
\n\n\n\n \n \n \"AdvancesPaper\n  \n \n \n \"Advances paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
@article{jiang_advances_2007,\n\ttitle = {Advances and challenges of nanotechnology-based drug delivery systems},\n\tvolume = {4},\n\tissn = {1742-5247},\n\turl = {https://doi.org/10.1517/17425247.4.6.621},\n\tdoi = {10.1517/17425247.4.6.621},\n\tabstract = {The ability to deliver highly efficient therapeutic compounds specifically to diseased sites is crucial for effectively treating all human illnesses. Unfortunately, conventional therapeutic strategies require unnecessarily high systemic administration due to non-specific biodistribution and rapid metabolism of free drug molecules prior to reaching their targeted sites. Using the tools of nanotechnology, drug delivery systems within the nanometer size regime can be developed to alter both pharmacological and therapeutic effects of drug molecules. Due to their small size, these novel DDS offer superior advantages, such as altered pharmacokinetic behaviour and improved payload, over traditional large-scale systems. In addition, the relative ease in modifying their surface chemistry permits the attachment of targeting and therapeutic molecules for specific therapeutic applications. Finally, complex nanostructures can be assembled using different building blocks with multiple functionalities ranging from targeting, detecting, imaging and therapeutic capabilities.},\n\tnumber = {6},\n\turldate = {2021-11-06},\n\tjournal = {Expert Opinion on Drug Delivery},\n\tauthor = {Jiang, Wen and Kim, Betty YS and Rutka, James T and Chan, Warren CW},\n\tmonth = nov,\n\tyear = {2007},\n\tpmid = {17970665},\n\tnote = {Publisher: Taylor \\& Francis\n\\_eprint: https://doi.org/10.1517/17425247.4.6.621},\n\tkeywords = {buckyballs, carbon nanotubes, drug delivery system, liposomes, nanostructures, quantum dots},\n\tpages = {621--633},\n\tfile = {Full Text PDF:files/2216/Jiang et al. - 2007 - Advances and challenges of nanotechnology-based dr.pdf:application/pdf;Snapshot:files/2217/17425247.4.6.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/Advances-and-challenges-of-nanotechnology-based-drug-delivery-systems-compressed.pdf}\n}\n\n
\n
\n\n\n
\n The ability to deliver highly efficient therapeutic compounds specifically to diseased sites is crucial for effectively treating all human illnesses. Unfortunately, conventional therapeutic strategies require unnecessarily high systemic administration due to non-specific biodistribution and rapid metabolism of free drug molecules prior to reaching their targeted sites. Using the tools of nanotechnology, drug delivery systems within the nanometer size regime can be developed to alter both pharmacological and therapeutic effects of drug molecules. Due to their small size, these novel DDS offer superior advantages, such as altered pharmacokinetic behaviour and improved payload, over traditional large-scale systems. In addition, the relative ease in modifying their surface chemistry permits the attachment of targeting and therapeutic molecules for specific therapeutic applications. Finally, complex nanostructures can be assembled using different building blocks with multiple functionalities ranging from targeting, detecting, imaging and therapeutic capabilities.\n
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\n \n\n \n \n \n \n \n \n Quantum dots as contrast agents for endoscopy: mathematical modeling and experimental validation of the optimal excitation wavelength.\n \n \n \n \n\n\n \n Roy, M., DaCosta, R. S., Weersink, R., Netchev, G., Davidson, S. R. H., Chan, W., & Wilson, B. C.\n\n\n \n\n\n\n In Colloidal Quantum Dots for Biomedical Applications II, volume 6448, pages 182–193, February 2007. SPIE\n \n\n\n\n
\n\n\n\n \n \n \"QuantumPaper\n  \n \n \n \"Quantum paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@inproceedings{roy_quantum_2007,\n\ttitle = {Quantum dots as contrast agents for endoscopy: mathematical modeling and experimental validation of the optimal excitation wavelength},\n\tvolume = {6448},\n\tshorttitle = {Quantum dots as contrast agents for endoscopy},\n\turl = {https://www.spiedigitallibrary.org/conference-proceedings-of-spie/6448/644812/Quantum-dots-as-contrast-agents-for-endoscopy--mathematical-modeling/10.1117/12.700954.full},\n\tdoi = {10.1117/12.700954},\n\tabstract = {Our group is investigating the use of ZnS-capped CdSe quantum dot (QD) bioconjugates combined with fluorescence endoscopy for improved early cancer detection in the esophagus, colon and lung. A major challenge in using fluorescent contrast agents in vivo is to extract the relevant signal from the tissue autofluorescence (AF). Our studies are aimed at maximizing the QD signal to AF background ratio (SBR) to facilitate detection. This work quantitatively evaluates the effect of the excitation wavelength on the SBR, using both experimental measurements and mathematical modeling. Experimental SBR measurements were done by imaging QD solutions placed onto (surface) or embedded in (sub-surface) ex vivo murine tissue samples (brain, kidney, liver, lung), using a polymethylmethacrylate (PMMA) microchannel phantom. The results suggest that the maximum contrast is reached when the excitation wavelength is set at 400±20 \\&mgr;m for the surface configuration. For the sub-surface configuration, the optimal excitation wavelength varies with the tissue type and QD emission wavelengths. Our mathematical model, based on an approximation to the diffusion equation, successfully predicts the optimal excitation wavelength for the surface configuration, but needs further modifications to be accurate in the sub-surface configuration.},\n\turldate = {2021-11-06},\n\tbooktitle = {Colloidal {Quantum} {Dots} for {Biomedical} {Applications} {II}},\n\tpublisher = {SPIE},\n\tauthor = {Roy, Mathieu and DaCosta, Ralph S. and Weersink, Robert and Netchev, George and Davidson, Sean R. H. and Chan, Warren and Wilson, Brian C.},\n\tmonth = feb,\n\tyear = {2007},\n\tpages = {182--193},\n\tfile = {Snapshot:files/2231/12.700954.html:text/html;Roy et al. - 2007 - Quantum dots as contrast agents for endoscopy mat.pdf:files/2232/Roy et al. - 2007 - Quantum dots as contrast agents for endoscopy mat.pdf:application/pdf},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/644812.pdf}\n}\n\n
\n
\n\n\n
\n Our group is investigating the use of ZnS-capped CdSe quantum dot (QD) bioconjugates combined with fluorescence endoscopy for improved early cancer detection in the esophagus, colon and lung. A major challenge in using fluorescent contrast agents in vivo is to extract the relevant signal from the tissue autofluorescence (AF). Our studies are aimed at maximizing the QD signal to AF background ratio (SBR) to facilitate detection. This work quantitatively evaluates the effect of the excitation wavelength on the SBR, using both experimental measurements and mathematical modeling. Experimental SBR measurements were done by imaging QD solutions placed onto (surface) or embedded in (sub-surface) ex vivo murine tissue samples (brain, kidney, liver, lung), using a polymethylmethacrylate (PMMA) microchannel phantom. The results suggest that the maximum contrast is reached when the excitation wavelength is set at 400±20 &mgr;m for the surface configuration. For the sub-surface configuration, the optimal excitation wavelength varies with the tissue type and QD emission wavelengths. Our mathematical model, based on an approximation to the diffusion equation, successfully predicts the optimal excitation wavelength for the surface configuration, but needs further modifications to be accurate in the sub-surface configuration.\n
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\n \n\n \n \n \n \n \n \n Quantitative detection of engineered nanoparticles in tissues and organs: An investigation of efficacy and linear dynamic ranges using ICP-AES.\n \n \n \n \n\n\n \n Fischer, H. C., Fournier-Bidoz, S., Chan, W. C. W., & Pang, K. S.\n\n\n \n\n\n\n Nanobiotechnol, 3(1): 46–54. March 2007.\n \n\n\n\n
\n\n\n\n \n \n \"QuantitativePaper\n  \n \n \n \"Quantitative paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{fischer_quantitative_2007,\n\ttitle = {Quantitative detection of engineered nanoparticles in tissues and organs: {An} investigation of efficacy and linear dynamic ranges using {ICP}-{AES}},\n\tvolume = {3},\n\tissn = {1551-1286, 1551-1294},\n\tshorttitle = {Quantitative detection of engineered nanoparticles in tissues and organs},\n\turl = {http://link.springer.com/10.1007/s12030-007-0006-2},\n\tdoi = {10.1007/s12030-007-0006-2},\n\tabstract = {The absence of effective non-isotopic quantification methods to determine in vivo nanoparticle kinetics and distribution is a key obstacle to the development of various biomedical nanotechnologies. This paper presents a novel adaptation of the established technology of Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) to a simple technique intended to address this obstacle. Applicability to three varieties of nanoparticles, (CdSe/ZnS quantum dots (QD), gold nanoparticles, and Fe304 nanopanicles) was investigated, and particle detection sensitivity was shown in moles of panicles per gram of tissue. Using gold nanoparticles, increased particle size corresponded with lower molar detection thresholds. Minimum linear detection ranges of 2.5 orders of magnitude for QDs and 1.5 orders of magnitude for all three sizes of gold were demonstrated. The detection of the Fe304 particles was hampered by the natural presence of Fe2+ in tissues, showing that the technique is not suitable for measuring nanoparticles composed of endogenous elements. These detection levels and ranges demonstrate that this technique is useful for quantifying nanoparticles in excised organs, after in vivo dosing.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2021-11-06},\n\tjournal = {Nanobiotechnol},\n\tauthor = {Fischer, H. C. and Fournier-Bidoz, S. and Chan, W. C. W. and Pang, K. S.},\n\tmonth = mar,\n\tyear = {2007},\n\tpages = {46--54},\n\tfile = {Fischer et al. - 2007 - Quantitative detection of engineered nanoparticles.pdf:files/2233/Fischer et al. - 2007 - Quantitative detection of engineered nanoparticles.pdf:application/pdf},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/Fischer2007_Article_QuantitativeDetectionOfEnginee.pdf}\n}\n\n
\n
\n\n\n
\n The absence of effective non-isotopic quantification methods to determine in vivo nanoparticle kinetics and distribution is a key obstacle to the development of various biomedical nanotechnologies. This paper presents a novel adaptation of the established technology of Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) to a simple technique intended to address this obstacle. Applicability to three varieties of nanoparticles, (CdSe/ZnS quantum dots (QD), gold nanoparticles, and Fe304 nanopanicles) was investigated, and particle detection sensitivity was shown in moles of panicles per gram of tissue. Using gold nanoparticles, increased particle size corresponded with lower molar detection thresholds. Minimum linear detection ranges of 2.5 orders of magnitude for QDs and 1.5 orders of magnitude for all three sizes of gold were demonstrated. The detection of the Fe304 particles was hampered by the natural presence of Fe2+ in tissues, showing that the technique is not suitable for measuring nanoparticles composed of endogenous elements. These detection levels and ranges demonstrate that this technique is useful for quantifying nanoparticles in excised organs, after in vivo dosing.\n
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\n \n\n \n \n \n \n \n \n Engineering Biocompatible Quantum Dots for Ultrasensitive, Real-Time Biological Imaging and Detection.\n \n \n \n \n\n\n \n Jiang, W., Singhal, A., Fischer, H., Mardyani, S., & Chan, W. C. W.\n\n\n \n\n\n\n In Ferrari, M., Desai, T., & Bhatia, S., editor(s), BioMEMS and Biomedical Nanotechnology: Volume III Therapeutic Micro/Nanotechnology, pages 137–156. Springer US, Boston, MA, 2007.\n \n\n\n\n
\n\n\n\n \n \n \"EngineeringPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
@incollection{jiang_engineering_2007,\n\taddress = {Boston, MA},\n\ttitle = {Engineering {Biocompatible} {Quantum} {Dots} for {Ultrasensitive}, {Real}-{Time} {Biological} {Imaging} and {Detection}},\n\tisbn = {978-0-387-25844-7},\n\turl = {https://doi.org/10.1007/978-0-387-25844-7_8},\n\tabstract = {Advances in the design of optical probes have played a central role in the emergence of photon-based microscopy techniques for biological imaging and detection [1, 2, 3, 4, 5, 6]. These advances have led to the elucidation of the biological function and activity of many proteins, nucleic acids, and other molecules in living cells, tissues, and animals. Currently, the molecular architecture of greater than 70\\% of all optical probes consists of an “optical emitter” attached to a “targeting molecule” [4]. The targeting molecule directs the optical emitter to specific biological sites where the optical emitter can then be used to detect the activities of biomolecules. The most popular optical probes have been traditionally designed from organic-based molecules; for instance, probes for the imaging of cellular cytoskeleton are based on the conjugation of red-fluorescent molecule Texas Red to the small targeting organic molecule phalloidin (for labeling actin fibers) and green-fluorescent Alexa Fluor 488 to a recognition antibody (for labeling microtubules) [4]. Hundreds of different types of organic-based fluorescent probes are commercially available. These probes can be used in numerous applications, including the staining of DNA and proteins, detection of subtle differences in the ionic content in living cells, or detection of protein structures [4, 7, 8, 9, 10]. Due to their complex molecular structures, however, organic fluorophores often exhibit unfavorable absorption and emission properties, such as photobleaching, environmental quenching, broad and asymmetric emission spectra, and the inability to excite multiple fluorophores of more than 2–3 colors at a single wavelength [10, 11].},\n\tlanguage = {en},\n\turldate = {2021-11-06},\n\tbooktitle = {{BioMEMS} and {Biomedical} {Nanotechnology}: {Volume} {III} {Therapeutic} {Micro}/{Nanotechnology}},\n\tpublisher = {Springer US},\n\tauthor = {Jiang, Wen and Singhal, Anupam and Fischer, Hans and Mardyani, Sawitri and Chan, Warren C. W.},\n\teditor = {Ferrari, Mauro and Desai, Tejal and Bhatia, Sangeeta},\n\tyear = {2007},\n\tdoi = {10.1007/978-0-387-25844-7_8},\n\tkeywords = {CdSe Nanocrystals, Maltose Binding Protein, Optical Probe, Sentinel Lymph Node, Sentinel Lymph Node Mapping},\n\tpages = {137--156},\n\tfile = {Springer Full Text PDF:files/2244/Jiang et al. - 2007 - Engineering Biocompatible Quantum Dots for Ultrase.pdf:application/pdf},\n}\n\n
\n
\n\n\n
\n Advances in the design of optical probes have played a central role in the emergence of photon-based microscopy techniques for biological imaging and detection [1, 2, 3, 4, 5, 6]. These advances have led to the elucidation of the biological function and activity of many proteins, nucleic acids, and other molecules in living cells, tissues, and animals. Currently, the molecular architecture of greater than 70% of all optical probes consists of an “optical emitter” attached to a “targeting molecule” [4]. The targeting molecule directs the optical emitter to specific biological sites where the optical emitter can then be used to detect the activities of biomolecules. The most popular optical probes have been traditionally designed from organic-based molecules; for instance, probes for the imaging of cellular cytoskeleton are based on the conjugation of red-fluorescent molecule Texas Red to the small targeting organic molecule phalloidin (for labeling actin fibers) and green-fluorescent Alexa Fluor 488 to a recognition antibody (for labeling microtubules) [4]. Hundreds of different types of organic-based fluorescent probes are commercially available. These probes can be used in numerous applications, including the staining of DNA and proteins, detection of subtle differences in the ionic content in living cells, or detection of protein structures [4, 7, 8, 9, 10]. Due to their complex molecular structures, however, organic fluorophores often exhibit unfavorable absorption and emission properties, such as photobleaching, environmental quenching, broad and asymmetric emission spectra, and the inability to excite multiple fluorophores of more than 2–3 colors at a single wavelength [10, 11].\n
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\n  \n 2006\n \n \n (11)\n \n \n
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\n \n\n \n \n \n \n \n \n Pharmacokinetics of Nanoscale Quantum Dots: In Vivo Distribution, Sequestration, and Clearance in the Rat.\n \n \n \n \n\n\n \n Fischer, H. C., Liu, L., Pang, K. S., & Chan, W. C. W.\n\n\n \n\n\n\n Advanced Functional Materials, 16(10): 1299–1305. 2006.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/adfm.200500529\n\n\n\n
\n\n\n\n \n \n \"PharmacokineticsPaper\n  \n \n \n \"Pharmacokinetics paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
@article{fischer_pharmacokinetics_2006,\n\ttitle = {Pharmacokinetics of {Nanoscale} {Quantum} {Dots}: {In} {Vivo} {Distribution}, {Sequestration}, and {Clearance} in the {Rat}},\n\tvolume = {16},\n\tissn = {1616-3028},\n\tshorttitle = {Pharmacokinetics of {Nanoscale} {Quantum} {Dots}},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/adfm.200500529},\n\tdoi = {10.1002/adfm.200500529},\n\tabstract = {Advances in nanotechnology research on quantum dots (QDs)—water soluble ZnS-capped, CdSe fluorescent semiconductor nanocrystals—for in vivo biomedical applications have prompted a close scrutiny of the behavior of nanostructures in vivo. Data pertaining to pharmacokinetics and toxicity will undoubtedly assist in designing better in vivo nanostructure contrast agents or therapies. In vivo kinetics, clearance, and metabolism of semiconductor QDs are characterized following their intravenous dosing in Sprague–Dawley rats. The QDs coated with the organic molecule mercaptoundecanoic acid and crosslinked with lysine (denoted as QD-LM) are cleared from plasma with a clearance of 0.59 ± 0.16 mL min–1 kg–1. A higher clearance (1.23 ± 0.22 mL min–1 kg–1) exists when the QDs are conjugated to bovine serum albumin (denoted as QD-BSA, P {\\textless} .05 (P = statistical significance). The biodistribution between these two QDs is also different. The liver takes up 40 \\% of the QD-LM dose and 99 \\% of QD-BSA dose after 90 min. Small amounts of both QDs appear in the spleen, kidney, and bone marrow. However, QDs are not detected in feces or urine for up to ten days after intravenous dosing.},\n\tlanguage = {en},\n\tnumber = {10},\n\turldate = {2021-11-06},\n\tjournal = {Advanced Functional Materials},\n\tauthor = {Fischer, H. C. and Liu, L. and Pang, K. S. and Chan, W. C. W.},\n\tyear = {2006},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/adfm.200500529},\n\tkeywords = {Biomedical applications, Core/shell nanoparticles, Nanocrystals, Nanotoxicology, Pharmacokinetics, semiconductor},\n\tpages = {1299--1305},\n\tfile = {Full Text PDF:files/2219/Fischer et al. - 2006 - Pharmacokinetics of Nanoscale Quantum Dots In Viv.pdf:application/pdf;Snapshot:files/2222/adfm.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/adfm.200500529.pdf}\n}\n\n
\n
\n\n\n
\n Advances in nanotechnology research on quantum dots (QDs)—water soluble ZnS-capped, CdSe fluorescent semiconductor nanocrystals—for in vivo biomedical applications have prompted a close scrutiny of the behavior of nanostructures in vivo. Data pertaining to pharmacokinetics and toxicity will undoubtedly assist in designing better in vivo nanostructure contrast agents or therapies. In vivo kinetics, clearance, and metabolism of semiconductor QDs are characterized following their intravenous dosing in Sprague–Dawley rats. The QDs coated with the organic molecule mercaptoundecanoic acid and crosslinked with lysine (denoted as QD-LM) are cleared from plasma with a clearance of 0.59 ± 0.16 mL min–1 kg–1. A higher clearance (1.23 ± 0.22 mL min–1 kg–1) exists when the QDs are conjugated to bovine serum albumin (denoted as QD-BSA, P \\textless .05 (P = statistical significance). The biodistribution between these two QDs is also different. The liver takes up 40 % of the QD-LM dose and 99 % of QD-BSA dose after 90 min. Small amounts of both QDs appear in the spleen, kidney, and bone marrow. However, QDs are not detected in feces or urine for up to ten days after intravenous dosing.\n
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\n \n\n \n \n \n \n \n \n Quantum Dots in Biological and Biomedical Research: Recent Progress and Present Challenges.\n \n \n \n \n\n\n \n Klostranec, J. M., & Chan, W. C. W.\n\n\n \n\n\n\n Advanced Materials, 18(15): 1953–1964. 2006.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.200500786\n\n\n\n
\n\n\n\n \n \n \"QuantumPaper\n  \n \n \n \"Quantum paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
@article{klostranec_quantum_2006,\n\ttitle = {Quantum {Dots} in {Biological} and {Biomedical} {Research}: {Recent} {Progress} and {Present} {Challenges}},\n\tvolume = {18},\n\tissn = {1521-4095},\n\tshorttitle = {Quantum {Dots} in {Biological} and {Biomedical} {Research}},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/adma.200500786},\n\tdoi = {10.1002/adma.200500786},\n\tabstract = {The marriage of nanomaterials with biology has produced a new generation of technologies that can profoundly impact biological and biomedical research. Quantum dots (Qdots) are an archetype for this hybrid research area and have gained popularity and interest from diverse research communities because of their unique and tunable optical properties. In this Review, we will describe their history and development, optical and electronic properties, and applications in biology and medicine. A critical evaluation of barriers impacting current Qdot technologies will be discussed and insights into the future outlook of the field will be explored.},\n\tlanguage = {en},\n\tnumber = {15},\n\turldate = {2021-11-06},\n\tjournal = {Advanced Materials},\n\tauthor = {Klostranec, J. M. and Chan, W. C. W.},\n\tyear = {2006},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.200500786},\n\tkeywords = {Biomedical materials, Bionanotechnology, Nanocrystals, Nanomedicine, semiconductor},\n\tpages = {1953--1964},\n\tfile = {Full Text PDF:files/2221/Klostranec and Chan - 2006 - Quantum Dots in Biological and Biomedical Research.pdf:application/pdf;Snapshot:files/2224/adma.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/adma.200500786.pdf}\n}\n\n
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\n\n\n
\n The marriage of nanomaterials with biology has produced a new generation of technologies that can profoundly impact biological and biomedical research. Quantum dots (Qdots) are an archetype for this hybrid research area and have gained popularity and interest from diverse research communities because of their unique and tunable optical properties. In this Review, we will describe their history and development, optical and electronic properties, and applications in biology and medicine. A critical evaluation of barriers impacting current Qdot technologies will be discussed and insights into the future outlook of the field will be explored.\n
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\n \n\n \n \n \n \n \n \n Optimizing the Synthesis of Red- to Near-IR-Emitting CdS-Capped CdTexSe1-x Alloyed Quantum Dots for Biomedical Imaging.\n \n \n \n \n\n\n \n Jiang, W., Singhal, A., Zheng, J., Wang, C., & Chan, W. C. W.\n\n\n \n\n\n\n Chem. Mater., 18(20): 4845–4854. October 2006.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"OptimizingPaper\n  \n \n \n \"Optimizing paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{jiang_optimizing_2006,\n\ttitle = {Optimizing the {Synthesis} of {Red}- to {Near}-{IR}-{Emitting} {CdS}-{Capped} {CdTexSe1}-x {Alloyed} {Quantum} {Dots} for {Biomedical} {Imaging}},\n\tvolume = {18},\n\tissn = {0897-4756},\n\turl = {https://doi.org/10.1021/cm061311x},\n\tdoi = {10.1021/cm061311x},\n\tabstract = {Advancements in biomedical imaging require the development of optical contrast agents at an emission region of low biological tissue absorbance, fluorescence, and scattering. This region occurs in the red to near-IR ({\\textgreater}600 nm) wavelength window. Quantum dots (Qdots) are excellent candidates for such applications. However, there are major challenges with developing high optical quality far-red- to near-IR-emitting Qdots (i.e., poor reproducibility, low quantum yield, and lack of photostability). Our aim is to systematically study how to prepare alloyed CdTexSe1-x with these properties. We discovered that the precursor concentrations of Te-to-Se and growth time had major impacts on the Qdot's optical properties. We also learned that the capping of these alloyed Qdots were difficult with ZnS but feasible with CdS because of the ZnS's lattice mismatch with the CdTexSe1-x. These systematic and basic studies led to the optimization of synthetic parameters for preparing Qdots with high quantum yield ({\\textgreater}30\\%), narrow fluorescence full width at half-maxima ({\\textless}50\\%), and stability against photobleaching ({\\textgreater}10 min under 100W Hg lamp excitation with a 1.4 numerical aperture 60× objective) for biomedical imaging and detection. We further demonstrate the conjugation of biorecognition molecules onto the surface of these alloyed Qdots and characterize their use as contrast agents in multicolored and ultrasensitive imaging.},\n\tnumber = {20},\n\turldate = {2021-11-06},\n\tjournal = {Chem. Mater.},\n\tauthor = {Jiang, Wen and Singhal, Anupam and Zheng, Jianing and Wang, Chen and Chan, Warren C. W.},\n\tmonth = oct,\n\tyear = {2006},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {4845--4854},\n\tfile = {Full Text PDF:files/2225/Jiang et al. - 2006 - Optimizing the Synthesis of Red- to Near-IR-Emitti.pdf:application/pdf;ACS Full Text Snapshot:files/2228/cm061311x.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/cm061311x.pdf}\n}\n\n
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\n Advancements in biomedical imaging require the development of optical contrast agents at an emission region of low biological tissue absorbance, fluorescence, and scattering. This region occurs in the red to near-IR (\\textgreater600 nm) wavelength window. Quantum dots (Qdots) are excellent candidates for such applications. However, there are major challenges with developing high optical quality far-red- to near-IR-emitting Qdots (i.e., poor reproducibility, low quantum yield, and lack of photostability). Our aim is to systematically study how to prepare alloyed CdTexSe1-x with these properties. We discovered that the precursor concentrations of Te-to-Se and growth time had major impacts on the Qdot's optical properties. We also learned that the capping of these alloyed Qdots were difficult with ZnS but feasible with CdS because of the ZnS's lattice mismatch with the CdTexSe1-x. These systematic and basic studies led to the optimization of synthetic parameters for preparing Qdots with high quantum yield (\\textgreater30%), narrow fluorescence full width at half-maxima (\\textless50%), and stability against photobleaching (\\textgreater10 min under 100W Hg lamp excitation with a 1.4 numerical aperture 60× objective) for biomedical imaging and detection. We further demonstrate the conjugation of biorecognition molecules onto the surface of these alloyed Qdots and characterize their use as contrast agents in multicolored and ultrasensitive imaging.\n
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\n \n\n \n \n \n \n \n \n High Throughput Quantification of Protein Expression of Cancer Antigens in Tissue Microarray Using Quantum Dot Nanocrystals.\n \n \n \n \n\n\n \n Ghazani, A. A., Lee, J. A., Klostranec, J., Xiang, Q., Dacosta, R. S., Wilson, B. C., Tsao, M. S., & Chan, W. C. W.\n\n\n \n\n\n\n Nano Lett., 6(12): 2881–2886. December 2006.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"HighPaper\n  \n \n \n \"High paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{ghazani_high_2006,\n\ttitle = {High {Throughput} {Quantification} of {Protein} {Expression} of {Cancer} {Antigens} in {Tissue} {Microarray} {Using} {Quantum} {Dot} {Nanocrystals}},\n\tvolume = {6},\n\tissn = {1530-6984},\n\turl = {https://doi.org/10.1021/nl062111n},\n\tdoi = {10.1021/nl062111n},\n\tabstract = {We developed and validated a novel method for quantifying protein expression of cancer tumors in an accurate, sensitive, and high throughput format. This technique integrates quantum dots, tissue microarray, optical spectroscopy, and algorithm design for analysis of tumor biopsies. The integration of this method for tissue analysis in the clinic bears potential impact for improving the diagnosis and treatment of cancer.},\n\tnumber = {12},\n\turldate = {2021-11-06},\n\tjournal = {Nano Lett.},\n\tauthor = {Ghazani, Arezou A. and Lee, Jeongjin A. and Klostranec, Jesse and Xiang, Qing and Dacosta, Ralph S. and Wilson, Brian C. and Tsao, Ming S. and Chan, Warren C. W.},\n\tmonth = dec,\n\tyear = {2006},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {2881--2886},\n\tfile = {Full Text PDF:files/2227/Ghazani et al. - 2006 - High Throughput Quantification of Protein Expressi.pdf:application/pdf;ACS Full Text Snapshot:files/2229/nl062111n.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nl062111n.pdf}\n}\n\n
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\n We developed and validated a novel method for quantifying protein expression of cancer tumors in an accurate, sensitive, and high throughput format. This technique integrates quantum dots, tissue microarray, optical spectroscopy, and algorithm design for analysis of tumor biopsies. The integration of this method for tissue analysis in the clinic bears potential impact for improving the diagnosis and treatment of cancer.\n
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\n \n\n \n \n \n \n \n \n Design of Biocompatible Chitosan Microgels for Targeted pH-Mediated Intracellular Release of Cancer Therapeutics.\n \n \n \n \n\n\n \n Zhang, H., Mardyani, S., Chan, W. C. W., & Kumacheva, E.\n\n\n \n\n\n\n Biomacromolecules, 7(5): 1568–1572. May 2006.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"DesignPaper\n  \n \n \n \"Design paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{zhang_design_2006,\n\ttitle = {Design of {Biocompatible} {Chitosan} {Microgels} for {Targeted} {pH}-{Mediated} {Intracellular} {Release} of {Cancer} {Therapeutics}},\n\tvolume = {7},\n\tissn = {1525-7797},\n\turl = {https://doi.org/10.1021/bm050912z},\n\tdoi = {10.1021/bm050912z},\n\tabstract = {We report the rational design of a chitosan-based drug delivery system. The chitosan derivative N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride (HTCC) was ionically cross-linked by sodium tripolyphosphate (TPP) to form sub-200-nm microgels that are responsive to pH changes. When these microgels were loaded with methotrexate disodium (MTX), a cytotoxic drug for cancer treatment, and conjugated to the targeting biomolecule apo-transferrin, a protein known to enter cells via receptor-mediated endocytosis, enhanced killing of immortalized HeLa cells was observed. In this intracellular delivery method, the microgel was exposed to low-pH environments that caused the chitosan to swell and release the drug. This rational drug delivery design may be useful in enhancing cancer therapy and reducing side effects.},\n\tnumber = {5},\n\turldate = {2021-11-06},\n\tjournal = {Biomacromolecules},\n\tauthor = {Zhang, Hong and Mardyani, Sawitri and Chan, Warren C. W. and Kumacheva, Eugenia},\n\tmonth = may,\n\tyear = {2006},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {1568--1572},\n\tfile = {Full Text PDF:files/2238/Zhang et al. - 2006 - Design of Biocompatible Chitosan Microgels for Tar.pdf:application/pdf;ACS Full Text Snapshot:files/2242/bm050912z.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/bm050912z.pdf}\n}\n\n
\n
\n\n\n
\n We report the rational design of a chitosan-based drug delivery system. The chitosan derivative N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride (HTCC) was ionically cross-linked by sodium tripolyphosphate (TPP) to form sub-200-nm microgels that are responsive to pH changes. When these microgels were loaded with methotrexate disodium (MTX), a cytotoxic drug for cancer treatment, and conjugated to the targeting biomolecule apo-transferrin, a protein known to enter cells via receptor-mediated endocytosis, enhanced killing of immortalized HeLa cells was observed. In this intracellular delivery method, the microgel was exposed to low-pH environments that caused the chitosan to swell and release the drug. This rational drug delivery design may be useful in enhancing cancer therapy and reducing side effects.\n
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\n \n\n \n \n \n \n \n \n Bionanotechnology Progress and Advances.\n \n \n \n \n\n\n \n Chan, W. C. W.\n\n\n \n\n\n\n Biology of Blood and Marrow Transplantation, 12(1, Supplement 1): 87–91. January 2006.\n \n\n\n\n
\n\n\n\n \n \n \"BionanotechnologyPaper\n  \n \n \n \"Bionanotechnology paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{chan_bionanotechnology_2006,\n\ttitle = {Bionanotechnology {Progress} and {Advances}},\n\tvolume = {12},\n\tissn = {1083-8791},\n\turl = {https://www.sciencedirect.com/science/article/pii/S1083879105006877},\n\tdoi = {10.1016/j.bbmt.2005.10.004},\n\tabstract = {Advances in the nanotechnology research have provided a new set of research tools, materials, structures, and systems for biological and medical research and applications. These nanotechnologies include the application of fluorescent quantum dots for optical imaging, the design of metallic nanoparticle surfaces for ultrasensitive biomolecular fingerprinting, and the use of nanostructures as hyperthermia agents for cancer therapy. Unlike conventional technologies, unique properties can be incorporated into nanometer-size particles, structures, and systems simply by changing their size, shape, and composition. Because of the tunable properties, biologists and clinicians could custom-design a material for a specific research need. In this review article, we highlight the recent advances and progress in Bionanotechnology research as well as provide future perspective on this integrative field.},\n\tlanguage = {en},\n\tnumber = {1, Supplement 1},\n\turldate = {2021-11-06},\n\tjournal = {Biology of Blood and Marrow Transplantation},\n\tauthor = {Chan, Warren C. W.},\n\tmonth = jan,\n\tyear = {2006},\n\tkeywords = {Bionanotechnology, Metallic nanostructures, Multifunctional nanodevices, Quantum dots},\n\tpages = {87--91},\n\tfile = {ScienceDirect Full Text PDF:files/2240/Chan - 2006 - Bionanotechnology Progress and Advances.pdf:application/pdf},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/1-s2.0-S1083879105006877-main.pdf}\n}\n\n
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\n Advances in the nanotechnology research have provided a new set of research tools, materials, structures, and systems for biological and medical research and applications. These nanotechnologies include the application of fluorescent quantum dots for optical imaging, the design of metallic nanoparticle surfaces for ultrasensitive biomolecular fingerprinting, and the use of nanostructures as hyperthermia agents for cancer therapy. Unlike conventional technologies, unique properties can be incorporated into nanometer-size particles, structures, and systems simply by changing their size, shape, and composition. Because of the tunable properties, biologists and clinicians could custom-design a material for a specific research need. In this review article, we highlight the recent advances and progress in Bionanotechnology research as well as provide future perspective on this integrative field.\n
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\n \n\n \n \n \n \n \n \n Cellular imaging and surface marker labeling of hematopoietic cells using quantum dot bioconjugates.\n \n \n \n \n\n\n \n Zheng, J., Ghazani, A. A, Song, Q., Mardyani, S., Chan, W. C W, & Wang, C.\n\n\n \n\n\n\n Lab Hematol, 12(2): 94–98. January 2006.\n \n\n\n\n
\n\n\n\n \n \n \"CellularPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{zheng_cellular_2006,\n\ttitle = {Cellular imaging and surface marker labeling of hematopoietic cells using quantum dot bioconjugates},\n\tvolume = {12},\n\tissn = {1523-6528},\n\turl = {https://doi.org/10.1532/LH96.04073},\n\tdoi = {10.1532/lh96.04073},\n\tabstract = {Semiconductor quantum dots (qdots) are emerging as a new class of fluorescent labels. The unique optical properties of qdots make them appealing in laboratory diagnosis; however, qdot-based probes remain to be developed and evaluated for clinical laboratory applications. In this study, 2 different approaches were employed to label hematopoietic cells with qdots. The first was based on a generalized intracellular delivery of qdots using qdot-transferrin conjugates through receptor-mediated endocytosis. Hematopoietic cells from umbilical cord blood or bone marrow were successfully labeled with qdot-transferrin in cell cultures. The fluorescence signal of qdot-transferrin was detected in the cytoplasmic location. The second approach was to use qdot-antibodies for labeling cell surface markers. The monoclonal antibodies to CD5, CD19, and CD45 surface antigens were conjugated to qdots with distinct emission spectra. The qdot-linked antibodies were shown to bind successfully to specific cell markers on lymphocytes. The signal obtained from the labeling of cells was detectable by using fluorescence microscopy and flow cytometry. The qdot signals were shown to be target specific, bright, and photo stable. The results of this study demonstrated the feasibility of using qdots for cell labeling and surface marker analysis of hematopoietic cells. Given the superior optical properties of qdots as compared to conventional fluorescence dyes, the qdot-based probe offers a promising tool for hematology analysis in clinical laboratories.},\n\tlanguage = {eng},\n\tnumber = {2},\n\turldate = {2021-11-06},\n\tjournal = {Lab Hematol},\n\tauthor = {Zheng, Jianing and Ghazani, Arezou A and Song, Qiang and Mardyani, Sawitri and Chan, Warren C W and Wang, Chen},\n\tmonth = jan,\n\tyear = {2006},\n\tpmid = {16751137},\n\tpages = {94--98},\n}\n\n
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\n Semiconductor quantum dots (qdots) are emerging as a new class of fluorescent labels. The unique optical properties of qdots make them appealing in laboratory diagnosis; however, qdot-based probes remain to be developed and evaluated for clinical laboratory applications. In this study, 2 different approaches were employed to label hematopoietic cells with qdots. The first was based on a generalized intracellular delivery of qdots using qdot-transferrin conjugates through receptor-mediated endocytosis. Hematopoietic cells from umbilical cord blood or bone marrow were successfully labeled with qdot-transferrin in cell cultures. The fluorescence signal of qdot-transferrin was detected in the cytoplasmic location. The second approach was to use qdot-antibodies for labeling cell surface markers. The monoclonal antibodies to CD5, CD19, and CD45 surface antigens were conjugated to qdots with distinct emission spectra. The qdot-linked antibodies were shown to bind successfully to specific cell markers on lymphocytes. The signal obtained from the labeling of cells was detectable by using fluorescence microscopy and flow cytometry. The qdot signals were shown to be target specific, bright, and photo stable. The results of this study demonstrated the feasibility of using qdots for cell labeling and surface marker analysis of hematopoietic cells. Given the superior optical properties of qdots as compared to conventional fluorescence dyes, the qdot-based probe offers a promising tool for hematology analysis in clinical laboratories.\n
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\n \n\n \n \n \n \n \n \n Biofunctionalized pH-Responsive Microgels for Cancer Cell Targeting: Rational Design.\n \n \n \n \n\n\n \n Das, M., Mardyani, S., Chan, W. C. W., & Kumacheva, E.\n\n\n \n\n\n\n Advanced Materials, 18(1): 80–83. 2006.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.200501043\n\n\n\n
\n\n\n\n \n \n \"BiofunctionalizedPaper\n  \n \n \n \"Biofunctionalized paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{das_biofunctionalized_2006,\n\ttitle = {Biofunctionalized {pH}-{Responsive} {Microgels} for {Cancer} {Cell} {Targeting}: {Rational} {Design}},\n\tvolume = {18},\n\tissn = {1521-4095},\n\tshorttitle = {Biofunctionalized {pH}-{Responsive} {Microgels} for {Cancer} {Cell} {Targeting}},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/adma.200501043},\n\tdoi = {10.1002/adma.200501043},\n\tabstract = {The design of a drug-delivery system based on bioconjugated, pH-responsive microgels is demonstrated. Microgels loaded with the anticancer drug Doxorubicin are introduced into the HeLa tumor cells by means of receptor- mediated endocytosis. Changes in pH within the intracellular environment induce shrinkage of microgels, triggering the drug release into the cells. The microgel described in this work shows enhanced cytotoxicity to HeLa cells (see Figure).},\n\tnumber = {1},\n\turldate = {2021-11-06},\n\tjournal = {Advanced Materials},\n\tauthor = {Das, M. and Mardyani, S. and Chan, W. C. W. and Kumacheva, E.},\n\tyear = {2006},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.200501043},\n\tkeywords = {Cells, Drug delivery, Microgels, Polymer gels},\n\tpages = {80--83},\n\tfile = {Full Text PDF:files/2246/Das et al. - 2006 - Biofunctionalized pH-Responsive Microgels for Canc.pdf:application/pdf;Snapshot:files/2248/adma.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/adma.200501043.pdf}\n}\n\n
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\n The design of a drug-delivery system based on bioconjugated, pH-responsive microgels is demonstrated. Microgels loaded with the anticancer drug Doxorubicin are introduced into the HeLa tumor cells by means of receptor- mediated endocytosis. Changes in pH within the intracellular environment induce shrinkage of microgels, triggering the drug release into the cells. The microgel described in this work shows enhanced cytotoxicity to HeLa cells (see Figure).\n
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\n \n\n \n \n \n \n \n \n Design and Characterization of Lysine Cross-Linked Mercapto-Acid Biocompatible Quantum Dots.\n \n \n \n \n\n\n \n Jiang, W., Mardyani, S., Fischer, H., & Chan, W. C. W.\n\n\n \n\n\n\n Chem. Mater., 18(4): 872–878. February 2006.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"DesignPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{jiang_design_2006,\n\ttitle = {Design and {Characterization} of {Lysine} {Cross}-{Linked} {Mercapto}-{Acid} {Biocompatible} {Quantum} {Dots}},\n\tvolume = {18},\n\tissn = {0897-4756},\n\turl = {https://doi.org/10.1021/cm051393+},\n\tdoi = {10.1021/cm051393+},\n\tabstract = {Semiconductor quantum dots (QDs) are a new generation of inorganic probes with advantageous properties over traditional organic-only probes for biological applications. A major hurdle in the use of QDs for biology is the inability of the hydrophobically synthesized QDs to interface with aqueous environments. There have been tremendous advances in the surface modification of hydrophobic QDs. However, none of the current techniques fits all of the criteria for an ideal QD coating for biological applications (e.g., maintain the small size and optical properties of QDs, have low nonspecific binding) while providing cost-effective, easy preparation on a large scale. We developed a highly stable biocompatible coating for the surface of ZnS-capped CdSe QDs that maintains all of the hydrophobic-coated QD optical properties. These QDs are prepared by first coating them with mercaptoundecanoic acid and are further cross-linked with the amino acid lysine in the presence of dicyclohexylcarbodiimide to form a stable hydrophilic shell. The surface contains carboxylic acid and amino functional groups for conjugation to biomolecules. Using a dynamic light scattering method, we found that the hydrodynamic diameter of these surface-modified QDs is approximately 20 nm. We demonstrated the feasibility of preparing {\\textgreater}400 mg of the biocompatible QDs and the successful conjugation of proteins onto their surface. Finally, we characterized the QD stability and optical properties in various biologically relevant environments.},\n\tnumber = {4},\n\turldate = {2021-11-06},\n\tjournal = {Chem. Mater.},\n\tauthor = {Jiang, Wen and Mardyani, Sawitri and Fischer, Hans and Chan, Warren C. W.},\n\tmonth = feb,\n\tyear = {2006},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {872--878},\n\tfile = {Full Text PDF:files/2249/Jiang et al. - 2006 - Design and Characterization of Lysine Cross-Linked.pdf:application/pdf;ACS Full Text Snapshot:files/2253/cm051393+.html:text/html},\n}\n\n
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\n Semiconductor quantum dots (QDs) are a new generation of inorganic probes with advantageous properties over traditional organic-only probes for biological applications. A major hurdle in the use of QDs for biology is the inability of the hydrophobically synthesized QDs to interface with aqueous environments. There have been tremendous advances in the surface modification of hydrophobic QDs. However, none of the current techniques fits all of the criteria for an ideal QD coating for biological applications (e.g., maintain the small size and optical properties of QDs, have low nonspecific binding) while providing cost-effective, easy preparation on a large scale. We developed a highly stable biocompatible coating for the surface of ZnS-capped CdSe QDs that maintains all of the hydrophobic-coated QD optical properties. These QDs are prepared by first coating them with mercaptoundecanoic acid and are further cross-linked with the amino acid lysine in the presence of dicyclohexylcarbodiimide to form a stable hydrophilic shell. The surface contains carboxylic acid and amino functional groups for conjugation to biomolecules. Using a dynamic light scattering method, we found that the hydrodynamic diameter of these surface-modified QDs is approximately 20 nm. We demonstrated the feasibility of preparing \\textgreater400 mg of the biocompatible QDs and the successful conjugation of proteins onto their surface. Finally, we characterized the QD stability and optical properties in various biologically relevant environments.\n
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\n \n\n \n \n \n \n \n \n Determining the Size and Shape Dependence of Gold Nanoparticle Uptake into Mammalian Cells.\n \n \n \n \n\n\n \n Chithrani, B. D., Ghazani, A. A., & Chan, W. C. W.\n\n\n \n\n\n\n Nano Lett., 6(4): 662–668. April 2006.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"DeterminingPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{chithrani_determining_2006,\n\ttitle = {Determining the {Size} and {Shape} {Dependence} of {Gold} {Nanoparticle} {Uptake} into {Mammalian} {Cells}},\n\tvolume = {6},\n\tissn = {1530-6984},\n\turl = {https://doi.org/10.1021/nl052396o},\n\tdoi = {10.1021/nl052396o},\n\tabstract = {We investigated the intracellular uptake of different sized and shaped colloidal gold nanoparticles. We showed that kinetics and saturation concentrations are highly dependent upon the physical dimensions of the nanoparticles (e.g., uptake half-life of 14, 50, and 74 nm nanoparticles is 2.10, 1.90, and 2.24 h, respectively). The findings from this study will have implications in the chemical design of nanostructures for biomedical applications (e.g., tuning intracellular delivery rates and amounts by nanoscale dimensions and engineering complex, multifunctional nanostructures for imaging and therapeutics).},\n\tnumber = {4},\n\turldate = {2021-11-06},\n\tjournal = {Nano Lett.},\n\tauthor = {Chithrani, B. Devika and Ghazani, Arezou A. and Chan, Warren C. W.},\n\tmonth = apr,\n\tyear = {2006},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {662--668},\n\tfile = {Full Text PDF:files/2251/Chithrani et al. - 2006 - Determining the Size and Shape Dependence of Gold .pdf:application/pdf;ACS Full Text Snapshot:files/2255/nl052396o.html:text/html},\n}\n\n
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\n We investigated the intracellular uptake of different sized and shaped colloidal gold nanoparticles. We showed that kinetics and saturation concentrations are highly dependent upon the physical dimensions of the nanoparticles (e.g., uptake half-life of 14, 50, and 74 nm nanoparticles is 2.10, 1.90, and 2.24 h, respectively). The findings from this study will have implications in the chemical design of nanostructures for biomedical applications (e.g., tuning intracellular delivery rates and amounts by nanoscale dimensions and engineering complex, multifunctional nanostructures for imaging and therapeutics).\n
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\n \n\n \n \n \n \n \n \n Nanoparticles in Biomedical Photonics.\n \n \n \n \n\n\n \n Chithrani, B. D., & Chan, W. C. W.\n\n\n \n\n\n\n In Wiley Encyclopedia of Biomedical Engineering. American Cancer Society, 2006.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/9780471740360.ebs0925\n\n\n\n
\n\n\n\n \n \n \"NanoparticlesPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@incollection{chithrani_nanoparticles_2006,\n\ttitle = {Nanoparticles in {Biomedical} {Photonics}},\n\tisbn = {978-0-471-74036-0},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/9780471740360.ebs0925},\n\tabstract = {Photonics refers to the studies or applications of light or photons, which includes the study and design of lasers, the applications of fluorophores in diagnostics, or the use of light-scattering technologies. Photonics is a broad research field. In this chapter, we will focus on an emerging subdiscipline of photonics, which is the development of gold nanostructures for biomedical applications. Gold nanostructures are of interest to the photonics community because these materials have interesting tunable optical properties. Biomedical engineers are exploiting these properties for development of new diagnostics, drug delivery, and therapeutics.},\n\tlanguage = {en},\n\turldate = {2021-11-06},\n\tbooktitle = {Wiley {Encyclopedia} of {Biomedical} {Engineering}},\n\tpublisher = {American Cancer Society},\n\tauthor = {Chithrani, B. Devika and Chan, Warren C. W.},\n\tyear = {2006},\n\tdoi = {10.1002/9780471740360.ebs0925},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/9780471740360.ebs0925},\n\tkeywords = {gold nanoparticles, nanotechnology, optical properties, photonics},\n\tfile = {Snapshot:files/2254/9780471740360.html:text/html},\n}\n\n
\n
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\n Photonics refers to the studies or applications of light or photons, which includes the study and design of lasers, the applications of fluorophores in diagnostics, or the use of light-scattering technologies. Photonics is a broad research field. In this chapter, we will focus on an emerging subdiscipline of photonics, which is the development of gold nanostructures for biomedical applications. Gold nanostructures are of interest to the photonics community because these materials have interesting tunable optical properties. Biomedical engineers are exploiting these properties for development of new diagnostics, drug delivery, and therapeutics.\n
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\n  \n 2005\n \n \n (3)\n \n \n
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\n \n\n \n \n \n \n \n \n Preliminary results: exploring the interactions of quantum dots with whole blood components.\n \n \n \n \n\n\n \n Fischer, H. C., Papa, E., Liu, L., Pang, K. S., & Chan, W. C. W.\n\n\n \n\n\n\n In Photonic Applications in Biosensing and Imaging, volume 5969, pages 54–59, October 2005. SPIE\n \n\n\n\n
\n\n\n\n \n \n \"PreliminaryPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@inproceedings{fischer_preliminary_2005,\n\ttitle = {Preliminary results: exploring the interactions of quantum dots with whole blood components},\n\tvolume = {5969},\n\tshorttitle = {Preliminary results},\n\turl = {https://www.spiedigitallibrary.org/conference-proceedings-of-spie/5969/59690E/Preliminary-results--exploring-the-interactions-of-quantum-dots-with/10.1117/12.629344.full},\n\tdoi = {10.1117/12.629344},\n\tabstract = {Biocompatible ZnS capped CdSe fluorescent semiconductor nanocrystals (quantum dots, QDs) exhibit great potential as imaging agents with biomedical and clinical relevance. However, little is known about the fate of the quantum dots \\textit{in vivo}, and the importance of chemical and physical composition that may influence their behavior \\textit{in vivo}. When the QDs are introduced \\textit{in vivo}, the first interactions with blood components will dictate their kinetic behavior \\textit{in vivo}. We present some preliminary results that demonstrate the interactions of the quantum dots with plasma proteins and that quantum dots can be trapped in fibrous networks.},\n\turldate = {2021-11-06},\n\tbooktitle = {Photonic {Applications} in {Biosensing} and {Imaging}},\n\tpublisher = {SPIE},\n\tauthor = {Fischer, Hans C. and Papa, Eliseo and Liu, Lichuan and Pang, K. Sandy and Chan, Warren C. W.},\n\tmonth = oct,\n\tyear = {2005},\n\tpages = {54--59},\n\tfile = {Snapshot:files/2266/12.629344.html:text/html},\n}\n\n
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\n Biocompatible ZnS capped CdSe fluorescent semiconductor nanocrystals (quantum dots, QDs) exhibit great potential as imaging agents with biomedical and clinical relevance. However, little is known about the fate of the quantum dots in vivo, and the importance of chemical and physical composition that may influence their behavior in vivo. When the QDs are introduced in vivo, the first interactions with blood components will dictate their kinetic behavior in vivo. We present some preliminary results that demonstrate the interactions of the quantum dots with plasma proteins and that quantum dots can be trapped in fibrous networks.\n
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\n \n\n \n \n \n \n \n \n Interfacing peptides identified using phage-display screening with quantum dots for the design of nanoprobes.\n \n \n \n \n\n\n \n Mardyani, S., Singhal, A., Jiang, W., & Chan, W. C. W.\n\n\n \n\n\n\n In Nanobiophotonics and Biomedical Applications II, volume 5705, pages 217–224, April 2005. SPIE\n \n\n\n\n
\n\n\n\n \n \n \"InterfacingPaper\n  \n \n \n \"Interfacing paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@inproceedings{mardyani_interfacing_2005,\n\ttitle = {Interfacing peptides identified using phage-display screening with quantum dots for the design of nanoprobes},\n\tvolume = {5705},\n\turl = {https://www.spiedigitallibrary.org/conference-proceedings-of-spie/5705/0000/Interfacing-peptides-identified-using-phage-display-screening-with-quantum-dots/10.1117/12.601609.full},\n\tdoi = {10.1117/12.601609},\n\tabstract = {The interface of targeting molecules that can recognize and identify specific biomolecules with highly luminescent semiconductor nanocrystals or quantum dots can lead to a novel and powerful new class of probes for studying biomolecules in real-time or for imaging and detecting diseases. We describe the rationale design of optical nanoprobes by using fluorescent semiconductor quantum dots with targeting molecules (TMs)-identified using phage display screening. Quantum dots are nanometer-sized particles with unique and tunable optical properties. They offer numerous optical advantages over traditional organic fluorophores in biological analysis and detection (e.g., photostability, continuous absorption profile).},\n\turldate = {2021-11-06},\n\tbooktitle = {Nanobiophotonics and {Biomedical} {Applications} {II}},\n\tpublisher = {SPIE},\n\tauthor = {Mardyani, Sawitri and Singhal, Anupam and Jiang, Wen and Chan, Warren C. W.},\n\tmonth = apr,\n\tyear = {2005},\n\tpages = {217--224},\n\tfile = {Snapshot:files/2269/12.601609.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/217.pdf}\n}\n\n
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\n The interface of targeting molecules that can recognize and identify specific biomolecules with highly luminescent semiconductor nanocrystals or quantum dots can lead to a novel and powerful new class of probes for studying biomolecules in real-time or for imaging and detecting diseases. We describe the rationale design of optical nanoprobes by using fluorescent semiconductor quantum dots with targeting molecules (TMs)-identified using phage display screening. Quantum dots are nanometer-sized particles with unique and tunable optical properties. They offer numerous optical advantages over traditional organic fluorophores in biological analysis and detection (e.g., photostability, continuous absorption profile).\n
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\n \n\n \n \n \n \n \n \n Surface-Plasmon-Coupled Emission of Quantum Dots.\n \n \n \n \n\n\n \n Gryczynski, I., Malicka, J., Jiang, W., Fischer, H., Chan, W. C. W., Gryczynski, Z., Grudzinski, W., & Lakowicz, J. R.\n\n\n \n\n\n\n J. Phys. Chem. B, 109(3): 1088–1093. January 2005.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"Surface-Plasmon-CoupledPaper\n  \n \n \n \"Surface-Plasmon-Coupled paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{gryczynski_surface-plasmon-coupled_2005,\n\ttitle = {Surface-{Plasmon}-{Coupled} {Emission} of {Quantum} {Dots}},\n\tvolume = {109},\n\tissn = {1520-6106},\n\turl = {https://doi.org/10.1021/jp046173i},\n\tdoi = {10.1021/jp046173i},\n\tabstract = {We studied surface plasmon-coupled emission (SPCE) of semiconductor quantum dots (QDs). These QDs are water-soluble ZnS-capped CdSe nanoparticles stabilized using lysine cross-linked mercaptoundecanoic acid. The QDs were spin-coated from 0.75\\% PVA solution on a glass slide covered with 50 nm of silver and a 5-nm protective SiO2 layer. Excited QDs induced surface plasmons in a thin silver layer. Surface plasmons emitted a hollow cone of radiation into an attached hemispherical glass prism at a narrow angle of 48.5°. This directional radiation (SPCE) preserves the spectral properties of QD emission and is highly p-polarized irrespective of the excitation polarization. The SPCE spectrum depends on the observation angle because of the intrinsic dispersive properties of SPCE phenomenon. The remarkable photostability can make QDs superior to organic fluorophores when long exposure to the intense excitation is needed. The nanosize QDs also introduce a roughness near the metal layer, which results in a many-fold increase of the coupling of the incident light to the surface plasmons. This scattered incident illumination transformed into directional, polarized radiation can be used simultaneously with SPCE to develop devices based on both quantum dot emission and light scattered from surface plasmons on a rough surface.},\n\tnumber = {3},\n\turldate = {2021-11-06},\n\tjournal = {J. Phys. Chem. B},\n\tauthor = {Gryczynski, Ignacy and Malicka, Joanna and Jiang, Wen and Fischer, Hans and Chan, Warren C. W. and Gryczynski, Zygmunt and Grudzinski, Wojciech and Lakowicz, Joseph R.},\n\tmonth = jan,\n\tyear = {2005},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {1088--1093},\n\tfile = {Full Text PDF:files/2270/Gryczynski et al. - 2005 - Surface-Plasmon-Coupled Emission of Quantum Dots.pdf:application/pdf;ACS Full Text Snapshot:files/2271/jp046173i.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/jp046173i.pdf}\n}\n\n
\n
\n\n\n
\n We studied surface plasmon-coupled emission (SPCE) of semiconductor quantum dots (QDs). These QDs are water-soluble ZnS-capped CdSe nanoparticles stabilized using lysine cross-linked mercaptoundecanoic acid. The QDs were spin-coated from 0.75% PVA solution on a glass slide covered with 50 nm of silver and a 5-nm protective SiO2 layer. Excited QDs induced surface plasmons in a thin silver layer. Surface plasmons emitted a hollow cone of radiation into an attached hemispherical glass prism at a narrow angle of 48.5°. This directional radiation (SPCE) preserves the spectral properties of QD emission and is highly p-polarized irrespective of the excitation polarization. The SPCE spectrum depends on the observation angle because of the intrinsic dispersive properties of SPCE phenomenon. The remarkable photostability can make QDs superior to organic fluorophores when long exposure to the intense excitation is needed. The nanosize QDs also introduce a roughness near the metal layer, which results in a many-fold increase of the coupling of the incident light to the surface plasmons. This scattered incident illumination transformed into directional, polarized radiation can be used simultaneously with SPCE to develop devices based on both quantum dot emission and light scattered from surface plasmons on a rough surface.\n
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\n  \n 2004\n \n \n (7)\n \n \n
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\n \n\n \n \n \n \n \n \n Assessing Porcine Liver-Derived Biomatrix for Hepatic Tissue Engineering.\n \n \n \n \n\n\n \n Lin, P., Chan, W. C., Badylak, S. F., & Bhatia, S. N.\n\n\n \n\n\n\n Tissue Engineering, 10(7-8): 1046–1053. July 2004.\n Publisher: Mary Ann Liebert, Inc., publishers\n\n\n\n
\n\n\n\n \n \n \"AssessingPaper\n  \n \n \n \"Assessing paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{lin_assessing_2004,\n\ttitle = {Assessing {Porcine} {Liver}-{Derived} {Biomatrix} for {Hepatic} {Tissue} {Engineering}},\n\tvolume = {10},\n\tissn = {1076-3279},\n\turl = {https://www.liebertpub.com/doi/abs/10.1089/ten.2004.10.1046},\n\tdoi = {10.1089/ten.2004.10.1046},\n\tabstract = {Acellular, biologically derived matrices such as small intestinal submucosa have been extensively utilized to induce tissue regeneration and remodeling of connective tissue, vascular grafts, and urinary bladder; however, decellularized scaffolds have not been explored for their potential utility in hepatic tissue engineering. In the case of both extracorporeal hepatocyte-based devices and implantable hepatocyte–scaffold tissue-engineered constructs, maintenance of hepatocellular function is of prime importance. In this study, we specifically explored decellularized, porcine, liver-derived biomatrix (LBM) as a bioresorbable scaffold for primary hepatocytes. Primary rat hepatocytes were cultured on LBM and compared with well-characterized hepatocyte culture models—double-gel cultures that promote maintenance of liver-specific functions for many weeks, and adsorbed collagen monolayers that lead to the rapid decline of hepatocellular function and viability. Hepatocytes were maintained for up to 45 days on LBM and liver-specific functions such as albumin synthesis, urea production, and P-450 IA1 activity were found to be significantly improved over adsorbed collagen cultures. Our data indicate that LBM may be a favorable alternative to existing scaffolds for tissue engineering in that it is bioresorbable, can be easily manipulated, and supports long-term hepatocellular functions in vitro.},\n\tnumber = {7-8},\n\turldate = {2021-11-06},\n\tjournal = {Tissue Engineering},\n\tauthor = {Lin, Paul and Chan, Warren C.W. and Badylak, Stephen F. and Bhatia, Sangeeta N.},\n\tmonth = jul,\n\tyear = {2004},\n\tnote = {Publisher: Mary Ann Liebert, Inc., publishers},\n\tpages = {1046--1053},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/ten.2004.10.1046.pdf}\n}\n\n
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\n\n\n
\n Acellular, biologically derived matrices such as small intestinal submucosa have been extensively utilized to induce tissue regeneration and remodeling of connective tissue, vascular grafts, and urinary bladder; however, decellularized scaffolds have not been explored for their potential utility in hepatic tissue engineering. In the case of both extracorporeal hepatocyte-based devices and implantable hepatocyte–scaffold tissue-engineered constructs, maintenance of hepatocellular function is of prime importance. In this study, we specifically explored decellularized, porcine, liver-derived biomatrix (LBM) as a bioresorbable scaffold for primary hepatocytes. Primary rat hepatocytes were cultured on LBM and compared with well-characterized hepatocyte culture models—double-gel cultures that promote maintenance of liver-specific functions for many weeks, and adsorbed collagen monolayers that lead to the rapid decline of hepatocellular function and viability. Hepatocytes were maintained for up to 45 days on LBM and liver-specific functions such as albumin synthesis, urea production, and P-450 IA1 activity were found to be significantly improved over adsorbed collagen cultures. Our data indicate that LBM may be a favorable alternative to existing scaffolds for tissue engineering in that it is bioresorbable, can be easily manipulated, and supports long-term hepatocellular functions in vitro.\n
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\n \n\n \n \n \n \n \n \n Intracellular Delivery of Quantum Dots for Live Cell Labeling and Organelle Tracking.\n \n \n \n \n\n\n \n Derfus, A. M., Chan, W. C. W., & Bhatia, S. N.\n\n\n \n\n\n\n Advanced Materials, 16(12): 961–966. 2004.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.200306111\n\n\n\n
\n\n\n\n \n \n \"IntracellularPaper\n  \n \n \n \"Intracellular paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{derfus_intracellular_2004,\n\ttitle = {Intracellular {Delivery} of {Quantum} {Dots} for {Live} {Cell} {Labeling} and {Organelle} {Tracking}},\n\tvolume = {16},\n\tissn = {1521-4095},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/adma.200306111},\n\tdoi = {10.1002/adma.200306111},\n\tabstract = {Several strategies borrowed from the field of gene delivery are adapted to enhance delivery of semiconductor quantum dots (QDs) to the interior of live cells. To traffic QDs to subcellular organelles, QDs were then derivatized with known peptide localization sequences, demonstrating the ability to target QDs to the nucleus and mitochondria (see Figure).},\n\tnumber = {12},\n\turldate = {2021-11-06},\n\tjournal = {Advanced Materials},\n\tauthor = {Derfus, A. M. and Chan, W. C. W. and Bhatia, S. N.},\n\tyear = {2004},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.200306111},\n\tkeywords = {Cytometry, Encapsulation, Nanoparticles, Quantum dots (QDs)},\n\tpages = {961--966},\n\tfile = {Full Text PDF:files/2258/Derfus et al. - 2004 - Intracellular Delivery of Quantum Dots for Live Ce.pdf:application/pdf;Snapshot:files/2259/adma.html:text/html},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/adma.200306111.pdf}\n}\n\n
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\n\n\n
\n Several strategies borrowed from the field of gene delivery are adapted to enhance delivery of semiconductor quantum dots (QDs) to the interior of live cells. To traffic QDs to subcellular organelles, QDs were then derivatized with known peptide localization sequences, demonstrating the ability to target QDs to the nucleus and mitochondria (see Figure).\n
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\n \n\n \n \n \n \n \n \n Trilayer hybrid polymer-quantum dot light-emitting diodes.\n \n \n \n \n\n\n \n Chaudhary, S., Ozkan, M., & Chan, W. C. W.\n\n\n \n\n\n\n Appl. Phys. Lett., 84(15): 2925–2927. April 2004.\n Publisher: American Institute of Physics\n\n\n\n
\n\n\n\n \n \n \"TrilayerPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{chaudhary_trilayer_2004,\n\ttitle = {Trilayer hybrid polymer-quantum dot light-emitting diodes},\n\tvolume = {84},\n\tissn = {0003-6951},\n\turl = {http://aip.scitation.org/doi/abs/10.1063/1.1699476},\n\tdoi = {10.1063/1.1699476},\n\tnumber = {15},\n\turldate = {2021-11-06},\n\tjournal = {Appl. Phys. Lett.},\n\tauthor = {Chaudhary, Sumit and Ozkan, Mihrimah and Chan, Warren C. W.},\n\tmonth = apr,\n\tyear = {2004},\n\tnote = {Publisher: American Institute of Physics},\n\tpages = {2925--2927},\n\tfile = {Full Text PDF:files/2261/Chaudhary et al. - 2004 - Trilayer hybrid polymer-quantum dot light-emitting.pdf:application/pdf},\n}\n\n
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\n \n\n \n \n \n \n \n \n Probing the Cytotoxicity of Semiconductor Quantum Dots.\n \n \n \n \n\n\n \n Derfus, A. M., Chan, W. C. W., & Bhatia, S. N.\n\n\n \n\n\n\n Nano Lett., 4(1): 11–18. January 2004.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"ProbingPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{derfus_probing_2004,\n\ttitle = {Probing the {Cytotoxicity} of {Semiconductor} {Quantum} {Dots}},\n\tvolume = {4},\n\tissn = {1530-6984},\n\turl = {https://doi.org/10.1021/nl0347334},\n\tdoi = {10.1021/nl0347334},\n\tabstract = {With their bright, photostable fluorescence, semiconductor quantum dots (QDs) show promise as alternatives to organic dyes for biological labeling. Questions about their potential cytotoxicity, however, remain unanswered. While cytotoxicity of bulk cadmium selenide (CdSe) is well documented, a number of groups have suggested that CdSe QDs are cytocompatible, at least with some immortalized cell lines. Using primary hepatocytes as a liver model, we found that CdSe-core QDs were indeed acutely toxic under certain conditions. Specifically, we found that the cytotoxicity of QDs was modulated by processing parameters during synthesis, exposure to ultraviolet light, and surface coatings. Our data further suggest that cytotoxicity correlates with the liberation of free Cd2+ ions due to deterioration of the CdSe lattice. When appropriately coated, CdSe-core QDs can be rendered nontoxic and used to track cell migration and reorganization in vitro. Our results provide information for design criteria for the use of QDs in vitro and especially in vivo, where deterioration over time may occur.},\n\tnumber = {1},\n\turldate = {2021-11-06},\n\tjournal = {Nano Lett.},\n\tauthor = {Derfus, Austin M. and Chan, Warren C. W. and Bhatia, Sangeeta N.},\n\tmonth = jan,\n\tyear = {2004},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {11--18},\n\tfile = {Full Text PDF:files/2263/Derfus et al. - 2004 - Probing the Cytotoxicity of Semiconductor Quantum .pdf:application/pdf;ACS Full Text Snapshot:files/2264/nl0347334.html:text/html},\n}\n\n
\n
\n\n\n
\n With their bright, photostable fluorescence, semiconductor quantum dots (QDs) show promise as alternatives to organic dyes for biological labeling. Questions about their potential cytotoxicity, however, remain unanswered. While cytotoxicity of bulk cadmium selenide (CdSe) is well documented, a number of groups have suggested that CdSe QDs are cytocompatible, at least with some immortalized cell lines. Using primary hepatocytes as a liver model, we found that CdSe-core QDs were indeed acutely toxic under certain conditions. Specifically, we found that the cytotoxicity of QDs was modulated by processing parameters during synthesis, exposure to ultraviolet light, and surface coatings. Our data further suggest that cytotoxicity correlates with the liberation of free Cd2+ ions due to deterioration of the CdSe lattice. When appropriately coated, CdSe-core QDs can be rendered nontoxic and used to track cell migration and reorganization in vitro. Our results provide information for design criteria for the use of QDs in vitro and especially in vivo, where deterioration over time may occur.\n
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\n \n\n \n \n \n \n \n \n Semiconductor quantum dots as contrast agents for whole animal imaging.\n \n \n \n \n\n\n \n Jiang, W., Papa, E., Fischer, H., Mardyani, S., & Chan, W. C. W.\n\n\n \n\n\n\n Trends in Biotechnology, 22(12): 607–609. December 2004.\n \n\n\n\n
\n\n\n\n \n \n \"SemiconductorPaper\n  \n \n \n \"Semiconductor paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
\n
@article{jiang_semiconductor_2004,\n\ttitle = {Semiconductor quantum dots as contrast agents for whole animal imaging},\n\tvolume = {22},\n\tissn = {0167-7799},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0167779904002999},\n\tdoi = {10.1016/j.tibtech.2004.10.012},\n\tabstract = {Recent developments in quantum dot (QD) technology have paved the way for using QDs as optical contrast agents for in vivo imaging. Pioneering papers showed the use of QDs as luminescent contrast agents for imaging cancer and guiding cancer surgery. The possible future use of QDs for clinical applications is expected to have a significant impact, however many challenges in this field have yet to be overcome.},\n\tlanguage = {en},\n\tnumber = {12},\n\turldate = {2021-11-06},\n\tjournal = {Trends in Biotechnology},\n\tauthor = {Jiang, Wen and Papa, Eli and Fischer, Hans and Mardyani, Sawitri and Chan, Warren C. W.},\n\tmonth = dec,\n\tyear = {2004},\n\tpages = {607--609},\n\tfile = {ScienceDirect Full Text PDF:files/2273/Jiang et al. - 2004 - Semiconductor quantum dots as contrast agents for .pdf:application/pdf},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/1-s2.0-S0167779904002999-main.pdf}\n}\n\n
\n
\n\n\n
\n Recent developments in quantum dot (QD) technology have paved the way for using QDs as optical contrast agents for in vivo imaging. Pioneering papers showed the use of QDs as luminescent contrast agents for imaging cancer and guiding cancer surgery. The possible future use of QDs for clinical applications is expected to have a significant impact, however many challenges in this field have yet to be overcome.\n
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\n \n\n \n \n \n \n \n \n Bioinspired Approaches to Building Nanoscale Devices.\n \n \n \n \n\n\n \n Mardyani, S., Jiang, W., Lai, J., Zhang, J., & Chan, W. C. W.\n\n\n \n\n\n\n In Stroscio, M. A., & Dutta, M., editor(s), Biological Nanostructures and Applications of Nanostructures in Biology: Electrical, Mechanical, and Optical Properties, of Bioelectric Engineering, pages 149–160. Springer US, Boston, MA, 2004.\n \n\n\n\n
\n\n\n\n \n \n \"BioinspiredPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@incollection{mardyani_bioinspired_2004,\n\taddress = {Boston, MA},\n\tseries = {Bioelectric {Engineering}},\n\ttitle = {Bioinspired {Approaches} to {Building} {Nanoscale} {Devices}},\n\tisbn = {978-0-306-48628-9},\n\turl = {https://doi.org/10.1007/0-306-48628-8_6},\n\tabstract = {ConclusionsThe field of nanotechnology has great potential to change the world. There has been a tremendous focus in the last thirty years on developing and characterizing nanostructure materials. Nowadays, the goal is to utilize these materials as precursors to build nanoscale devices and to develop novel approaches to assemble these precursor nanostructurs into a functional device. Biology offers an excellent guide for assembling nanostructures since a cell can produce thousands of different functional units with only 20-different amino acid building blocks. Biomolecules such as proteins, oligonucleotides and microbial systems have been successfully applied toward organizing nanostructures into macrostructures. Although we have not built complex and functional nanostructures, there are numerous examples in the literature that demonstrate the utility of simple monofunctional nanostructures for biosensing and imaging applications, and drug storage/release systems. In the future, the ability to assemble nanostructures into complex functional units should produce novel systems that will have a broad and significant impact.},\n\tlanguage = {en},\n\turldate = {2021-11-06},\n\tbooktitle = {Biological {Nanostructures} and {Applications} of {Nanostructures} in {Biology}: {Electrical}, {Mechanical}, and {Optical} {Properties}},\n\tpublisher = {Springer US},\n\tauthor = {Mardyani, Sawitri and Jiang, Wen and Lai, Jonathan and Zhang, Jane and Chan, Warren C. W.},\n\teditor = {Stroscio, Michael A. and Dutta, Mitra},\n\tyear = {2004},\n\tdoi = {10.1007/0-306-48628-8_6},\n\tkeywords = {American Chemical Society, Gold Nanoparticles, Lower Critical Solution Temperature, Nanoparticle Assembly, Phage Particle},\n\tpages = {149--160},\n\tfile = {Springer Full Text PDF:files/2275/Mardyani et al. - 2004 - Bioinspired Approaches to Building Nanoscale Devic.pdf:application/pdf},\n}\n\n
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\n ConclusionsThe field of nanotechnology has great potential to change the world. There has been a tremendous focus in the last thirty years on developing and characterizing nanostructure materials. Nowadays, the goal is to utilize these materials as precursors to build nanoscale devices and to develop novel approaches to assemble these precursor nanostructurs into a functional device. Biology offers an excellent guide for assembling nanostructures since a cell can produce thousands of different functional units with only 20-different amino acid building blocks. Biomolecules such as proteins, oligonucleotides and microbial systems have been successfully applied toward organizing nanostructures into macrostructures. Although we have not built complex and functional nanostructures, there are numerous examples in the literature that demonstrate the utility of simple monofunctional nanostructures for biosensing and imaging applications, and drug storage/release systems. In the future, the ability to assemble nanostructures into complex functional units should produce novel systems that will have a broad and significant impact.\n
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\n \n\n \n \n \n \n \n \n Biomedical Applications of Semiconductor Quantum Dots.\n \n \n \n \n\n\n \n Singhal, A., Fischer, H. C., Wong, J., & Chan, W. C. W.\n\n\n \n\n\n\n In Stroscio, M. A., & Dutta, M., editor(s), Biological Nanostructures and Applications of Nanostructures in Biology: Electrical, Mechanical, and Optical Properties, of Bioelectric Engineering, pages 37–50. Springer US, Boston, MA, 2004.\n \n\n\n\n
\n\n\n\n \n \n \"BiomedicalPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@incollection{singhal_biomedical_2004,\n\taddress = {Boston, MA},\n\tseries = {Bioelectric {Engineering}},\n\ttitle = {Biomedical {Applications} of {Semiconductor} {Quantum} {Dots}},\n\tisbn = {978-0-306-48628-9},\n\turl = {https://doi.org/10.1007/0-306-48628-8_2},\n\tlanguage = {en},\n\turldate = {2021-11-06},\n\tbooktitle = {Biological {Nanostructures} and {Applications} of {Nanostructures} in {Biology}: {Electrical}, {Mechanical}, and {Optical} {Properties}},\n\tpublisher = {Springer US},\n\tauthor = {Singhal, Anupam and Fischer, Hans C. and Wong, Johnson and Chan, Warren C. W.},\n\teditor = {Stroscio, Michael A. and Dutta, Mitra},\n\tyear = {2004},\n\tdoi = {10.1007/0-306-48628-8_2},\n\tkeywords = {Biological Application, Dimethyl Cadmium, Organic Fluorophores, Quantum Yield, Semiconductor Nanocrystals},\n\tpages = {37--50},\n\tfile = {Springer Full Text PDF:files/2277/Singhal et al. - 2004 - Biomedical Applications of Semiconductor Quantum D.pdf:application/pdf},\n}\n\n
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\n  \n 2003\n \n \n (1)\n \n \n
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\n \n\n \n \n \n \n \n \n Semiconductor Quantum Dots as Multicolor and Ultrasensitive Biological Labels.\n \n \n \n \n\n\n \n Chan, W. C. W., Gao, X., & Nie, S.\n\n\n \n\n\n\n In Colloids and Colloid Assemblies, pages 494–506. John Wiley & Sons, Ltd, 2003.\n Section: 16 _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/3527602100.ch16\n\n\n\n
\n\n\n\n \n \n \"SemiconductorPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
\n
@incollection{chan_semiconductor_2003,\n\ttitle = {Semiconductor {Quantum} {Dots} as {Multicolor} and {Ultrasensitive} {Biological} {Labels}},\n\tisbn = {978-3-527-60210-0},\n\turl = {http://onlinelibrary.wiley.com/doi/abs/10.1002/3527602100.ch16},\n\tabstract = {This chapter contains sections titled: Introduction Synthesis and Surface Chemistry Optical Properties Applications in Biology and Medicine Conclusions Acknowledgements},\n\tlanguage = {en},\n\turldate = {2021-11-06},\n\tbooktitle = {Colloids and {Colloid} {Assemblies}},\n\tpublisher = {John Wiley \\& Sons, Ltd},\n\tauthor = {Chan, Warren C. W. and Gao, Xiaohu and Nie, Shuming},\n\tyear = {2003},\n\tdoi = {10.1002/3527602100.ch16},\n\tnote = {Section: 16\n\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/3527602100.ch16},\n\tkeywords = {multicolor, semiconductor quantum dots, surface, synthesis, ultrasensitive biological labels},\n\tpages = {494--506},\n\tfile = {Full Text PDF:files/2279/Chan et al. - 2003 - Semiconductor Quantum Dots as Multicolor and Ultra.pdf:application/pdf;Snapshot:files/2280/3527602100.html:text/html},\n}\n\n
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\n This chapter contains sections titled: Introduction Synthesis and Surface Chemistry Optical Properties Applications in Biology and Medicine Conclusions Acknowledgements\n
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\n  \n 2002\n \n \n (3)\n \n \n
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\n \n\n \n \n \n \n \n \n Quantum-dot nanocrystals for ultrasensitive biological labeling and multicolor optical encoding.\n \n \n \n \n\n\n \n Gao, X., Chan, W. C. W., & Nie, S.\n\n\n \n\n\n\n JBO, 7(4): 532–537. October 2002.\n Publisher: SPIE\n\n\n\n
\n\n\n\n \n \n \"Quantum-dotPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{gao_quantum-dot_2002,\n\ttitle = {Quantum-dot nanocrystals for ultrasensitive biological labeling and multicolor optical encoding},\n\tvolume = {7},\n\tissn = {1083-3668, 1560-2281},\n\turl = {https://www.spiedigitallibrary.org/journals/journal-of-biomedical-optics/volume-7/issue-4/0000/Quantum-dot-nanocrystals-for-ultrasensitive-biological-labeling-and-multicolor-optical/10.1117/1.1506706.full},\n\tdoi = {10.1117/1.1506706},\n\tabstract = {The \\textit{Journal of Biomedical Optics} (JBO) is an open access journal that publishes peer-reviewed papers on the use of novel optical systems and techniques for improved health care and biomedical research.},\n\tnumber = {4},\n\turldate = {2021-11-06},\n\tjournal = {JBO},\n\tauthor = {Gao, Xiaohu and Chan, Warren C. W. and Nie, Shuming},\n\tmonth = oct,\n\tyear = {2002},\n\tnote = {Publisher: SPIE},\n\tpages = {532--537},\n\tfile = {Full Text PDF:files/2282/Gao et al. - 2002 - Quantum-dot nanocrystals for ultrasensitive biolog.pdf:application/pdf;Snapshot:files/2284/1.1506706.html:text/html},\n}\n\n
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\n The Journal of Biomedical Optics (JBO) is an open access journal that publishes peer-reviewed papers on the use of novel optical systems and techniques for improved health care and biomedical research.\n
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\n \n\n \n \n \n \n \n \n Nanocrystal targeting in vivo.\n \n \n \n \n\n\n \n Åkerman, M. E., Chan, W. C. W., Laakkonen, P., Bhatia, S. N., & Ruoslahti, E.\n\n\n \n\n\n\n PNAS, 99(20): 12617–12621. October 2002.\n Publisher: National Academy of Sciences Section: Biological Sciences\n\n\n\n
\n\n\n\n \n \n \"NanocrystalPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{akerman_nanocrystal_2002,\n\ttitle = {Nanocrystal targeting in vivo},\n\tvolume = {99},\n\tcopyright = {Copyright © 2002, The National Academy of Sciences},\n\tissn = {0027-8424, 1091-6490},\n\turl = {http://www.pnas.org/content/99/20/12617},\n\tdoi = {10.1073/pnas.152463399},\n\tabstract = {Inorganic nanostructures that interface with biological systems have recently attracted widespread interest in biology and medicine. Nanoparticles are thought to have potential as novel intravascular probes for both diagnostic (e.g., imaging) and therapeutic purposes (e.g., drug delivery). Critical issues for successful nanoparticle delivery include the ability to target specific tissues and cell types and escape from the biological particulate filter known as the reticuloendothelial system. We set out to explore the feasibility of in vivo targeting by using semiconductor quantum dots (qdots). Qdots are small ({\\textless}10 nm) inorganic nanocrystals that possess unique luminescent properties; their fluorescence emission is stable and tuned by varying the particle size or composition. We show that ZnS-capped CdSe qdots coated with a lung-targeting peptide accumulate in the lungs of mice after i.v. injection, whereas two other peptides specifically direct qdots to blood vessels or lymphatic vessels in tumors. We also show that adding polyethylene glycol to the qdot coating prevents nonselective accumulation of qdots in reticuloendothelial tissues. These results encourage the construction of more complex nanostructures with capabilities such as disease sensing and drug delivery.},\n\tlanguage = {en},\n\tnumber = {20},\n\turldate = {2021-11-06},\n\tjournal = {PNAS},\n\tauthor = {Åkerman, Maria E. and Chan, Warren C. W. and Laakkonen, Pirjo and Bhatia, Sangeeta N. and Ruoslahti, Erkki},\n\tmonth = oct,\n\tyear = {2002},\n\tpmid = {12235356},\n\tnote = {Publisher: National Academy of Sciences\nSection: Biological Sciences},\n\tpages = {12617--12621},\n\tfile = {Full Text PDF:files/2285/Åkerman et al. - 2002 - Nanocrystal targeting in vivo.pdf:application/pdf;Snapshot:files/2288/12617.html:text/html},\n}\n\n
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\n\n\n
\n Inorganic nanostructures that interface with biological systems have recently attracted widespread interest in biology and medicine. Nanoparticles are thought to have potential as novel intravascular probes for both diagnostic (e.g., imaging) and therapeutic purposes (e.g., drug delivery). Critical issues for successful nanoparticle delivery include the ability to target specific tissues and cell types and escape from the biological particulate filter known as the reticuloendothelial system. We set out to explore the feasibility of in vivo targeting by using semiconductor quantum dots (qdots). Qdots are small (\\textless10 nm) inorganic nanocrystals that possess unique luminescent properties; their fluorescence emission is stable and tuned by varying the particle size or composition. We show that ZnS-capped CdSe qdots coated with a lung-targeting peptide accumulate in the lungs of mice after i.v. injection, whereas two other peptides specifically direct qdots to blood vessels or lymphatic vessels in tumors. We also show that adding polyethylene glycol to the qdot coating prevents nonselective accumulation of qdots in reticuloendothelial tissues. These results encourage the construction of more complex nanostructures with capabilities such as disease sensing and drug delivery.\n
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\n \n\n \n \n \n \n \n \n Luminescent quantum dots for multiplexed biological detection and imaging.\n \n \n \n \n\n\n \n Chan, W. C. W, Maxwell, D. J, Gao, X., Bailey, R. E, Han, M., & Nie, S.\n\n\n \n\n\n\n Current Opinion in Biotechnology, 13(1): 40–46. February 2002.\n \n\n\n\n
\n\n\n\n \n \n \"LuminescentPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@article{chan_luminescent_2002,\n\ttitle = {Luminescent quantum dots for multiplexed biological detection and imaging},\n\tvolume = {13},\n\tissn = {0958-1669},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0958166902002823},\n\tdoi = {10.1016/S0958-1669(02)00282-3},\n\tabstract = {Recent advances in nanomaterials have produced a new class of fluorescent labels by conjugating semiconductor quantum dots with biorecognition molecules. These nanometer-sized conjugates are water-soluble and biocompatible, and provide important advantages over organic dyes and lanthanide probes. In particular, the emission wavelength of quantum-dot nanocrystals can be continuously tuned by changing the particle size, and a single light source can be used for simultaneous excitation of all different-sized dots. High-quality dots are also highly stable against photobleaching and have narrow, symmetric emission spectra. These novel optical properties render quantum dots ideal fluorophores for ultrasensitive, multicolor, and multiplexing applications in molecular biotechnology and bioengineering.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2021-11-06},\n\tjournal = {Current Opinion in Biotechnology},\n\tauthor = {Chan, Warren C. W and Maxwell, Dustin J and Gao, Xiaohu and Bailey, Robert E and Han, Mingyong and Nie, Shuming},\n\tmonth = feb,\n\tyear = {2002},\n\tkeywords = {cells, fluorescence, genes, multiplexing, optical encoding, proteins, quantum dots, ultrasensitive},\n\tpages = {40--46},\n\tfile = {ScienceDirect Full Text PDF:files/2289/Chan et al. - 2002 - Luminescent quantum dots for multiplexed biologica.pdf:application/pdf;ScienceDirect Snapshot:files/2290/S0958166902002823.html:text/html},\n}\n\n
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\n\n\n
\n Recent advances in nanomaterials have produced a new class of fluorescent labels by conjugating semiconductor quantum dots with biorecognition molecules. These nanometer-sized conjugates are water-soluble and biocompatible, and provide important advantages over organic dyes and lanthanide probes. In particular, the emission wavelength of quantum-dot nanocrystals can be continuously tuned by changing the particle size, and a single light source can be used for simultaneous excitation of all different-sized dots. High-quality dots are also highly stable against photobleaching and have narrow, symmetric emission spectra. These novel optical properties render quantum dots ideal fluorophores for ultrasensitive, multicolor, and multiplexing applications in molecular biotechnology and bioengineering.\n
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\n  \n 2000\n \n \n (4)\n \n \n
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\n \n\n \n \n \n \n \n \n Probing Single Molecules in Single Living Cells.\n \n \n \n \n\n\n \n Byassee, T. A., Chan, W. C. W., & Nie, S.\n\n\n \n\n\n\n Anal. Chem., 72(22): 5606–5611. November 2000.\n Publisher: American Chemical Society\n\n\n\n
\n\n\n\n \n \n \"ProbingPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{byassee_probing_2000,\n\ttitle = {Probing {Single} {Molecules} in {Single} {Living} {Cells}},\n\tvolume = {72},\n\tissn = {0003-2700},\n\turl = {https://doi.org/10.1021/ac000705j},\n\tdoi = {10.1021/ac000705j},\n\tabstract = {Single-molecule detection in single living cells has been achieved by using confocal fluorescence microscopy and externally tagged probe molecules. The intracellular background fluorescence is substantially higher than that in aqueous buffer, but this background is continuous and stable and does not significantly interfere with the measurement of single-molecule photon bursts. As a result, single-molecule data have been obtained on three types of fluorescent probes at spatially resolved locations (e.g., cytoplasm and nucleus) inside human HeLa cells. First, the iron transport protein transferrin labeled with tetramethylrhodamine undergoes rapid receptor-mediated endocytosis, and single transferrin molecules are detected inside living cells. Second, the cationic dye rhodamine 6G (R6G) enters cultured cells by a potential-driven process, and single R6G molecules are observed as intense photon bursts when they move in and out of the intracellular laser beam. Third, we report results on synthetic oligonucleotides that are tagged with a fluorescent dye and are taken up by living cells via a passive, nonendocytic pathway.},\n\tnumber = {22},\n\turldate = {2021-11-06},\n\tjournal = {Anal. Chem.},\n\tauthor = {Byassee, Tyler A. and Chan, Warren C. W. and Nie, Shuming},\n\tmonth = nov,\n\tyear = {2000},\n\tnote = {Publisher: American Chemical Society},\n\tpages = {5606--5611},\n\tfile = {Full Text PDF:files/2292/Byassee et al. - 2000 - Probing Single Molecules in Single Living Cells.pdf:application/pdf;ACS Full Text Snapshot:files/2296/ac000705j.html:text/html},\n}\n\n
\n
\n\n\n
\n Single-molecule detection in single living cells has been achieved by using confocal fluorescence microscopy and externally tagged probe molecules. The intracellular background fluorescence is substantially higher than that in aqueous buffer, but this background is continuous and stable and does not significantly interfere with the measurement of single-molecule photon bursts. As a result, single-molecule data have been obtained on three types of fluorescent probes at spatially resolved locations (e.g., cytoplasm and nucleus) inside human HeLa cells. First, the iron transport protein transferrin labeled with tetramethylrhodamine undergoes rapid receptor-mediated endocytosis, and single transferrin molecules are detected inside living cells. Second, the cationic dye rhodamine 6G (R6G) enters cultured cells by a potential-driven process, and single R6G molecules are observed as intense photon bursts when they move in and out of the intracellular laser beam. Third, we report results on synthetic oligonucleotides that are tagged with a fluorescent dye and are taken up by living cells via a passive, nonendocytic pathway.\n
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\n \n\n \n \n \n \n \n \n One-step conjugation of biomolecules to luminescent nanocrystals.\n \n \n \n \n\n\n \n Chan, W. C. W., Prendergast, T. L., Jain, M., & Nie, S.\n\n\n \n\n\n\n In Molecular Imaging: Reporters, Dyes, Markers, and Instrumentation, volume 3924, pages 2–9, April 2000. SPIE\n \n\n\n\n
\n\n\n\n \n \n \"One-stepPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@inproceedings{chan_one-step_2000,\n\ttitle = {One-step conjugation of biomolecules to luminescent nanocrystals},\n\tvolume = {3924},\n\turl = {https://www.spiedigitallibrary.org/conference-proceedings-of-spie/3924/0000/One-step-conjugation-of-biomolecules-to-luminescent-nanocrystals/10.1117/12.384243.full},\n\tdoi = {10.1117/12.384243},\n\tabstract = {The development of optical pulses is crucial to the elucidation of complex biological and chemical problems. Existing fluorescent labels tend to photobleach, have low luminescence, and area sensitive to the environment. These problems can be overcome by the use of semiconductor quantum dots. These ZnS-capped CdSe quantum dots are synthesized in an organic media. To use them for biological labeling, the quantum dots are made water-soluble by adsorbing bifunctional molecules onto the surface. This step is crucial for the successful conjugation of biomolecules onto the surface. In this report, a new method for the direct adsorption of biomolecules onto the surface of quantum dots is demonstrated. Biomolecules such as glutathione, mercaptusuccic acid, and histidine are directly conjugated to luminescent quantum dots by S-Zn or N-Zn bonding.},\n\turldate = {2021-11-06},\n\tbooktitle = {Molecular {Imaging}: {Reporters}, {Dyes}, {Markers}, and {Instrumentation}},\n\tpublisher = {SPIE},\n\tauthor = {Chan, Warren C. W. and Prendergast, Tara L. and Jain, Manas and Nie, Shuming},\n\tmonth = apr,\n\tyear = {2000},\n\tpages = {2--9},\n\tfile = {Snapshot:files/2295/12.384243.html:text/html},\n}\n\n
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\n The development of optical pulses is crucial to the elucidation of complex biological and chemical problems. Existing fluorescent labels tend to photobleach, have low luminescence, and area sensitive to the environment. These problems can be overcome by the use of semiconductor quantum dots. These ZnS-capped CdSe quantum dots are synthesized in an organic media. To use them for biological labeling, the quantum dots are made water-soluble by adsorbing bifunctional molecules onto the surface. This step is crucial for the successful conjugation of biomolecules onto the surface. In this report, a new method for the direct adsorption of biomolecules onto the surface of quantum dots is demonstrated. Biomolecules such as glutathione, mercaptusuccic acid, and histidine are directly conjugated to luminescent quantum dots by S-Zn or N-Zn bonding.\n
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\n \n\n \n \n \n \n \n \n Single molecule detection in single living cells.\n \n \n \n \n\n\n \n Byassee, T. A., Chan, W. C. W., & Nie, S.\n\n\n \n\n\n\n In Scanning and Force Microscopies for Biomedical Applications II, volume 3922, pages 2–10, April 2000. SPIE\n \n\n\n\n
\n\n\n\n \n \n \"SinglePaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@inproceedings{byassee_single_2000,\n\ttitle = {Single molecule detection in single living cells},\n\tvolume = {3922},\n\turl = {https://www.spiedigitallibrary.org/conference-proceedings-of-spie/3922/0000/Single-molecule-detection-in-single-living-cells/10.1117/12.383337.full},\n\tdoi = {10.1117/12.383337},\n\tabstract = {The ability to detect a single analyte molecule represents the ultimate in sensitivity. Single molecule detection has emerged as a powerful tool to characterize heterogeneous systems, in which traditional bulk sampling methods provide a signal averaged over a large number of analytes. Traditionally, single molecule measurements have required highly controlled experimental conditions using ultrapure solvents to create a minimum level of interference. These constraints have primarily limited this technique to examination of systems in vitro. In this report we present the first instance of real-time single molecule detection in living cells. Our experimental approach allows dynamic monitoring of individual fluorophores in vivo, despite the highly complex cellular environment.},\n\turldate = {2021-11-06},\n\tbooktitle = {Scanning and {Force} {Microscopies} for {Biomedical} {Applications} {II}},\n\tpublisher = {SPIE},\n\tauthor = {Byassee, Tyler A. and Chan, Warren C. W. and Nie, Shuming},\n\tmonth = apr,\n\tyear = {2000},\n\tpages = {2--10},\n\tfile = {Snapshot:files/2298/12.383337.html:text/html},\n}\n\n
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\n The ability to detect a single analyte molecule represents the ultimate in sensitivity. Single molecule detection has emerged as a powerful tool to characterize heterogeneous systems, in which traditional bulk sampling methods provide a signal averaged over a large number of analytes. Traditionally, single molecule measurements have required highly controlled experimental conditions using ultrapure solvents to create a minimum level of interference. These constraints have primarily limited this technique to examination of systems in vitro. In this report we present the first instance of real-time single molecule detection in living cells. Our experimental approach allows dynamic monitoring of individual fluorophores in vivo, despite the highly complex cellular environment.\n
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\n \n\n \n \n \n \n \n \n Luminescent Quantum Dots for Ultrasensitive Medical Diagnostics.\n \n \n \n \n\n\n \n Chan, W. C. W., Prendergast, T., Bailey, R., Gao, X., & Nie, S.\n\n\n \n\n\n\n In Biomedical Optical Spectroscopy and Diagnostics (2000), paper SuA4, pages SuA4, April 2000. Optical Society of America\n \n\n\n\n
\n\n\n\n \n \n \"LuminescentPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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@inproceedings{chan_luminescent_2000,\n\ttitle = {Luminescent {Quantum} {Dots} for {Ultrasensitive} {Medical} {Diagnostics}},\n\tcopyright = {© 2000 Optical Society of America},\n\turl = {https://www.osapublishing.org/abstract.cfm?uri=BOSD-2000-SuA4},\n\tdoi = {10.1364/BOSD.2000.SuA4},\n\tabstract = {Highly luminescent semiconductor quantum dots (ZnS-capped CdSe) have been covalently coupled to bio molecules for use in ultra sensitive biological detection (Science 281, 2016-2018, 1998, and C\\&amp;EN News, Sept. 28 issue, 1998).},\n\tlanguage = {EN},\n\turldate = {2021-11-06},\n\tbooktitle = {Biomedical {Optical} {Spectroscopy} and {Diagnostics} (2000), paper {SuA4}},\n\tpublisher = {Optical Society of America},\n\tauthor = {Chan, Warren C. W. and Prendergast, Tara and Bailey, Robert and Gao, Xiaohu and Nie, Shunting},\n\tmonth = apr,\n\tyear = {2000},\n\tkeywords = {Cadmium selenide, Clinical applications, Fluorescence, Linewidth, Molecules, Quantum dots},\n\tpages = {SuA4},\n\tfile = {Full Text PDF:files/2299/Chan et al. - 2000 - Luminescent Quantum Dots for Ultrasensitive Medica.pdf:application/pdf;Snapshot:files/2303/abstract.html:text/html},\n}\n\n
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\n Highly luminescent semiconductor quantum dots (ZnS-capped CdSe) have been covalently coupled to bio molecules for use in ultra sensitive biological detection (Science 281, 2016-2018, 1998, and C&EN News, Sept. 28 issue, 1998).\n
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\n  \n 1999\n \n \n (2)\n \n \n
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\n \n\n \n \n \n \n \n \n Single-virus analysis by correlated optical spectroscopy and atomic force microscopy.\n \n \n \n \n\n\n \n Chan, W. C. W., & Nie, S.\n\n\n \n\n\n\n In Scanning and Force Microscopies for Biomedical Applications, volume 3607, pages 52–59, June 1999. SPIE\n \n\n\n\n
\n\n\n\n \n \n \"Single-virusPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@inproceedings{chan_single-virus_1999,\n\ttitle = {Single-virus analysis by correlated optical spectroscopy and atomic force microscopy},\n\tvolume = {3607},\n\turl = {https://www.spiedigitallibrary.org/conference-proceedings-of-spie/3607/0000/Single-virus-analysis-by-correlated-optical-spectroscopy-and-atomic-force/10.1117/12.350617.full},\n\tdoi = {10.1117/12.350617},\n\tabstract = {Single adeno- and tobacco mosaic viruses have been studied by correlated fluorescence spectroscopy and tapping-mode atomic force microscopy. The size and shape of spatially isolated, fluorescently tagged viruses are measured on the nanometer scale, and the fluorescent labels in each virus are determined by wavelength-resolved spectroscopy. This work extends ultrasensitive measurement to the single-virus level and is expected to have applications in studying gene therapy vectors and virus-cell interactions.},\n\turldate = {2021-11-06},\n\tbooktitle = {Scanning and {Force} {Microscopies} for {Biomedical} {Applications}},\n\tpublisher = {SPIE},\n\tauthor = {Chan, Warren C. W. and Nie, Shuming},\n\tmonth = jun,\n\tyear = {1999},\n\tpages = {52--59},\n\tfile = {Snapshot:files/2302/12.350617.html:text/html},\n}\n\n
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\n Single adeno- and tobacco mosaic viruses have been studied by correlated fluorescence spectroscopy and tapping-mode atomic force microscopy. The size and shape of spatially isolated, fluorescently tagged viruses are measured on the nanometer scale, and the fluorescent labels in each virus are determined by wavelength-resolved spectroscopy. This work extends ultrasensitive measurement to the single-virus level and is expected to have applications in studying gene therapy vectors and virus-cell interactions.\n
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\n \n\n \n \n \n \n \n \n Single-virus analysis by correlated optical spectroscopy and atomic force microscopy.\n \n \n \n \n\n\n \n Chan, W. C. W., & Nie, S.\n\n\n \n\n\n\n In Scanning and Force Microscopies for Biomedical Applications, volume 3607, pages 52–59, June 1999. SPIE\n \n\n\n\n
\n\n\n\n \n \n \"Single-virusPaper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n  \n \n abstract \n \n\n \n  \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@inproceedings{chan_single-virus_1999-1,\n\ttitle = {Single-virus analysis by correlated optical spectroscopy and atomic force microscopy},\n\tvolume = {3607},\n\turl = {https://www.spiedigitallibrary.org/conference-proceedings-of-spie/3607/0000/Single-virus-analysis-by-correlated-optical-spectroscopy-and-atomic-force/10.1117/12.350617.full},\n\tdoi = {10.1117/12.350617},\n\tabstract = {Single adeno- and tobacco mosaic viruses have been studied by correlated fluorescence spectroscopy and tapping-mode atomic force microscopy. The size and shape of spatially isolated, fluorescently tagged viruses are measured on the nanometer scale, and the fluorescent labels in each virus are determined by wavelength-resolved spectroscopy. This work extends ultrasensitive measurement to the single-virus level and is expected to have applications in studying gene therapy vectors and virus-cell interactions.},\n\turldate = {2021-11-06},\n\tbooktitle = {Scanning and {Force} {Microscopies} for {Biomedical} {Applications}},\n\tpublisher = {SPIE},\n\tauthor = {Chan, Warren C. W. and Nie, Shuming},\n\tmonth = jun,\n\tyear = {1999},\n\tpages = {52--59},\n\tfile = {Snapshot:files/2305/12.350617.html:text/html},\n}\n\n
\n
\n\n\n
\n Single adeno- and tobacco mosaic viruses have been studied by correlated fluorescence spectroscopy and tapping-mode atomic force microscopy. The size and shape of spatially isolated, fluorescently tagged viruses are measured on the nanometer scale, and the fluorescent labels in each virus are determined by wavelength-resolved spectroscopy. This work extends ultrasensitive measurement to the single-virus level and is expected to have applications in studying gene therapy vectors and virus-cell interactions.\n
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\n  \n 1998\n \n \n (1)\n \n \n
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\n \n\n \n \n \n \n \n \n Quantum Dot Bioconjugates for Ultrasensitive Nonisotopic Detection.\n \n \n \n \n\n\n \n Chan, W. C. W., & Nie, S.\n\n\n \n\n\n\n Science, 281(5385): 2016–2018. September 1998.\n Publisher: American Association for the Advancement of Science\n\n\n\n
\n\n\n\n \n \n \"QuantumPaper\n  \n \n \n \"Quantum paper\n  \n \n\n \n \n doi\n  \n \n\n \n link\n  \n \n\n bibtex\n \n\n \n\n \n  \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n  \n \n \n\n\n\n
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@article{chan_quantum_1998,\n\ttitle = {Quantum {Dot} {Bioconjugates} for {Ultrasensitive} {Nonisotopic} {Detection}},\n\tvolume = {281},\n\turl = {https://www.science.org/doi/10.1126/science.281.5385.2016},\n\tdoi = {10.1126/science.281.5385.2016},\n\tnumber = {5385},\n\turldate = {2021-11-06},\n\tjournal = {Science},\n\tauthor = {Chan, Warren C. W. and Nie, Shuming},\n\tmonth = sep,\n\tyear = {1998},\n\tnote = {Publisher: American Association for the Advancement of Science},\n\tpages = {2016--2018},\n\turl_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/2016.full_.pdf}\n}\n
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