The dose threshold for nanoparticle tumour delivery
Top Cited Papers
- 30 November 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Materials
- Vol. 19 (12), 1362-+
- https://doi.org/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. 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.Keywords
Funding Information
- Gouvernement du Canada | Canadian Institutes of Health Research (PJT-148848)
- Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (2015-06397)
- Terry Fox Research Institute
- Canada Research Chairs (950-223924)
- Princess Margaret Cancer Foundation
- Canadian Cancer Society Research Institute (706286)
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