@article{ouyang_dose_2020,
	title = {The dose threshold for nanoparticle tumour delivery},
	volume = {19},
	copyright = {2020 The Author(s), under exclusive licence to Springer Nature Limited},
	issn = {1476-4660},
	url = {https://www.nature.com/articles/s41563-020-0755-z},
	doi = {10.1038/s41563-020-0755-z},
	abstract = {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.},
	language = {en},
	number = {12},
	urldate = {2021-11-06},
	journal = {Nat. Mater.},
	author = {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.},
	month = dec,
	year = {2020},
	note = {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},
	keywords = {Cancer therapy, Nanoparticles},
	pages = {1362--1371},
	file = {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},
	url_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2022/01/Ouyang-et-al.-2020-The-dose-threshold-for-nanoparticle-tumour-deliver.pdf}
}

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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.","language":"en","number":"12","urldate":"2021-11-06","journal":"Nat. 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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. 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