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

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.

Product Number
Product Description

Sodium citrate tribasic dihydrate, ACS reagent, ≥99.0%
Gold(III) chloride hydrate, 99.995% trace metals basis
Hydroquinone, ReagentPlus®, 99%
CellCrown inserts, 6 well plate inserts with 1.0 μm polycarbonate filter, sterile
Collagenase from Clostridium histolyticum, suitable for release of physiologically active rat hepatocytes, Type IV, 0.5-5.0 FALGPA units/mg solid, ≥125 CDU/mg solid
Cholesterol, Sigma Grade, ≥99%
Formalin solution, neutral buffered, 10%, histological tissue fixative
1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid, ≥97.0% (CHN)