期刊
NATURE MATERIALS
卷 19, 期 12, 页码 1362-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41563-020-0755-z
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资金
- Canadian Cancer Society [502200, 706286]
- Canadian Institutes of Health Research [PJT-148848, FDN-159932]
- Natural Sciences and Engineering Research Council of Canada [2015-06397]
- Canada Research Chair Program [950-223924, 950-232468]
- Canada Foundation for Innovation [21765]
- Princess Margaret Cancer Foundation
- Vanier Canada Graduate Scholarship
- CIHR
- McLaughlin Centre
- Ontario Graduate Scholarships
- Institute of Biomaterials and Biomedical Engineering
- University of Toronto School of Graduate Studies
- Donnelly Centre
- Frank Fletcher Memorial Fund
- OGS
- University of Toronto Faculty of Applied Science and Engineering
- NSERC
- Wildcat Foundation
- Ontario Graduate Scholarship
- Paul and Sally Wang fellowships
- Wildcat Fellows Program
- Royal Bank of Canada
- Borealis AI
- Department of Defense Ovarian Cancer Research Program
- Terry Fox Research Institute
- University of Toronto Faculty of Medicine
- Walter C. Sumner foundation
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. Efficient nanoparticle delivery into tumours has been a challenge in the field. It is now shown that the efficiency can be improved substantially when the dose breaches a specific threshold.
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