| Literature DB >> 32778816 |
Wilson Poon1,2, Yi-Nan Zhang1,2, Ben Ouyang3,1,2, Zachary P Lin1,2, Benjamin R Kingston1,2, Anthony J Tavares1,2,4, Yuwei Zhang2,5, Juan Chen6, Michael S Valic6, Abdullah M Syed1,2,7, Presley MacMillan2,5, Julien Couture-Senécal1,2,8, Gang Zheng1,6,9, Warren C W Chan10,11,12,13,14.
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.Entities:
Mesh：
Substances：
Year: 2020 PMID： 32778816 DOI： 10.1038/s41563-020-0755-z
Source DB: PubMed Journal: Nat Mater ISSN： 1476-1122 Impact factor: 43.841