An erythrocyte-delivered photoactivatable oxaliplatin nanoprodrug for enhanced antitumor efficacy and immune response

The outcome of conventional platinum (Pt)-based chemotherapy is limited by reduced circulation, failure to accumulate in the tumor, and dose-limiting toxicity arising from non-controllable activation. To address these limitations, we present an erythrocyte-delivered and near-infrared (NIR) photoactivatable Pt^IV nanoprodrug for advanced cancer treatment. Compared with small molecule Pt^IV prodrugs, this nanoprodrug exhibits significantly enhanced stability, prolonged circulation in the blood, and minimized side effects. The hitchhiking of the nanoprodrug on erythrocytes dramatically increases Pt accumulation in the tumor. Upon irradiation, the nanoprodrug releases oxaliplatin in a controllable manner, resulting in significant antitumor activity against breast tumors in vivo, as evidenced by the complete elimination of tumors from a single-dose injection. Additionally, this nanoprodrug is associated with remarkably enhanced immunopotentiation. Our study highlights an efficient strategy to overcome the shortcomings of traditional Pt-based chemotherapy via the erythrocyte-mediated delivery of an NIR-activatable nanoprodrug of oxaliplatin, a clinically used anticancer drug.