Enhancing Circulation and Tumor Accumulation of Carboplatin via an Erythrocyte-Anchored Prodrug Strategy.

Abstract

The short circulatory half-lives and low tumor accumulation of carboplatin greatly limit the drug's efficacy in vivo. Herein, we address these challenges by using a prodrug strategy and present the rational design of a novel platinum(IV) anticancer prodrug that can hitchhike on erythrocytes. This prodrug, designated as ERY1-PtIV , can bind to erythrocytes efficiently and stably, possessing a circulatory half-life 18.5 times longer than that of carboplatin in mice. This elongated circulatory half-life enables platinum to accumulate at levels 7.7 times higher than with carboplatin, with steady levels in the tumors. As a consequence, the ERY1-PtIV prodrug is proved to exhibit significantly enhanced antitumor activity and reduced side effects compared with carboplatin. Collectively, our novel approach highlights an efficient strategy to utilize intrinsic erythrocytes as auto-binding carriers to enhance the tumor accumulation and subsequent antitumor efficacy of platinum drugs.