Merck

The dose threshold for nanoparticle tumour delivery.

Nature materials (2020-08-12)
Ben Ouyang, Wilson Poon, Yi-Nan Zhang, Zachary P Lin, Benjamin R Kingston, Anthony J Tavares, Yuwei Zhang, Juan Chen, Michael S Valic, Abdullah M Syed, Presley MacMillan, Julien Couture-Senécal, Gang Zheng, Warren C W Chan
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.

MATERIALS
Product Number
Brand
Product Description

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