@article{tsoi_mechanism_2016,
	title = {Mechanism of hard-nanomaterial clearance by the liver},
	volume = {15},
	copyright = {2016 Nature Publishing Group},
	issn = {1476-4660},
	url = {https://www.nature.com/articles/nmat4718},
	doi = {10.1038/nmat4718},
	abstract = {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.},
	language = {en},
	number = {11},
	urldate = {2021-11-06},
	journal = {Nature Mater},
	author = {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.},
	month = nov,
	year = {2016},
	note = {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},
	keywords = {Drug delivery, Nanoparticles},
	pages = {1212--1221},
	file = {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},
	url_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nmat4718-min.pdf}
}

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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.","language":"en","number":"11","urldate":"2021-11-06","journal":"Nature Mater","author":[{"propositions":[],"lastnames":["Tsoi"],"firstnames":["Kim","M."],"suffixes":[]},{"propositions":[],"lastnames":["MacParland"],"firstnames":["Sonya","A."],"suffixes":[]},{"propositions":[],"lastnames":["Ma"],"firstnames":["Xue-Zhong"],"suffixes":[]},{"propositions":[],"lastnames":["Spetzler"],"firstnames":["Vinzent","N."],"suffixes":[]},{"propositions":[],"lastnames":["Echeverri"],"firstnames":["Juan"],"suffixes":[]},{"propositions":[],"lastnames":["Ouyang"],"firstnames":["Ben"],"suffixes":[]},{"propositions":[],"lastnames":["Fadel"],"firstnames":["Saleh","M."],"suffixes":[]},{"propositions":[],"lastnames":["Sykes"],"firstnames":["Edward","A."],"suffixes":[]},{"propositions":[],"lastnames":["Goldaracena"],"firstnames":["Nicolas"],"suffixes":[]},{"propositions":[],"lastnames":["Kaths"],"firstnames":["Johann","M."],"suffixes":[]},{"propositions":[],"lastnames":["Conneely"],"firstnames":["John","B."],"suffixes":[]},{"propositions":[],"lastnames":["Alman"],"firstnames":["Benjamin","A."],"suffixes":[]},{"propositions":[],"lastnames":["Selzner"],"firstnames":["Markus"],"suffixes":[]},{"propositions":[],"lastnames":["Ostrowski"],"firstnames":["Mario","A."],"suffixes":[]},{"propositions":[],"lastnames":["Adeyi"],"firstnames":["Oyedele","A."],"suffixes":[]},{"propositions":[],"lastnames":["Zilman"],"firstnames":["Anton"],"suffixes":[]},{"propositions":[],"lastnames":["McGilvray"],"firstnames":["Ian","D."],"suffixes":[]},{"propositions":[],"lastnames":["Chan"],"firstnames":["Warren","C.","W."],"suffixes":[]}],"month":"November","year":"2016","note":"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","keywords":"Drug delivery, Nanoparticles","pages":"1212–1221","file":"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","url_paper":"https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/nmat4718-min.pdf","bibtex":"@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. 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