Facile synthesis of GSH-triggered degradable hyperbranched polymer coprodrug as unimolecular micelles for precise tumor combination chemotherapy

Abstract

Combination chemotherapy has attracted more intense attention in tumor treatment, in which the drug-loading mode and drug proportion of the nano drug co-delivery system (NDCDS) play an important role in the anti-tumor efficacy. Here, GSH-triggered degradable hyperbranched polymer coprodrugs were designed via the self-condensing vinyl polymerization (SCVP) of the polymerizable prodrug monomers and poly(ethylene glycol) methacrylate (PEGMA) with a GSH-sensitive inimer. The drug proportion of the polymer coprodrugs could be easily adjusted by altering the feeding ratio for a better synergistic effect. The proposed polymer coprodrugs could form unimolecular micelles and be degraded completely to release the two parent drugs (DOX and CPT) responding to the high-level GSH in the tumor cells with a very low drug premature leakage in the intercellular environment and a low mis-release in the normal cells. The optimized one, HBPP-DOX/CPT-5, possessed a low CI50 of 0.11, showing promising potential in safe and effective tumor combination chemotherapy.