Reactive Oxygen Species-Activatable Camptothecin Polyprodrugs Based Dextran Enhances Chemotherapy Efficacy by Damaging Mitochondria
Low loading capacity, poor accumulation rate and weak permeability in tumor sites have been identified as the critical barrier for anti-cancer nanomedicines (ANMs). We herein reported a reactive oxygen species (ROS)-activatable ANMs of dextran-b-P(CPTMA-co-OEGMA) (DCPT). It aimed to meet above challenges for improving the therapeutic efficiency of chemotherapy. In this system, the camptothecin (CPT) was selected as a chemotherapy drug and poly (ethylene glycol) methyl ether methacrylate (OEGMA) played a role of hydrophilic block to enhance the water solubility of polyprodrug micelles. In the high ROS levels in the tumor microenvironment, micelles could be disassembled, and simultaneously, the anti-cancer drug of CPT would be released from the DCPT micelles. The 4T1-tumor growth would be greatly inhibited by these two DCPT polyprodrugs, with outstanding in vivo biosafety. The results of both in vitro and in vivo studies indicated the superior therapeutic effects of DCPT. The rational design of polyprodrug nanomedicine may be served as a promising strategy for the development of tumor microenvironment-responsive ANMs, thus improving chemotherapy efficacy.