Above the dose threshold: a simple way to improve the delivery efficiency of nanomedicine

摘要

Recently, a paper by Warren Chan et al. published in NatureMaterials, discovered a simple way to improve the tumordelivery efficiency by reaching a nanomedicine dose above athreshold.1 As the largest organ of the reticuloendothelialsystem, the liver takes up majority of nanomedicine afteringestion.2 This dose threshold is based on the kinetic balancebetween the uptake of nanomedicine in the liver and theabsorption in the tumor, which is related to the number ofreceptors and binding sites available on Kupffer cells residing inthe liver (Fig. 1). A dose exceeding the effective binding sitethreshold overwhelmed the Kupffer cells, therefore it can reducethe liver clearance of nanomedicine and prolong the circulation.To investigate the mechanisms, three magnitude orders (50billion to 50 trillion) of nanoparticles were injected into 4T1 tumorbearingBALB/c mice. Chan et al. found that the plasma half-life ofnanoparticles extended as the dose increased, demonstrating thathigh-dose could significantly reduce the hepatic clearance. Inaddition, after a single dose of more than 1 trillion, the uptake ofnanoparticles by Kupffer cells was restricted within 24 h, whichwas unrelated to Kupffer cell death nor accelerated bloodclearance (ABC) phenomenon.