Facile synthesis of GSH-triggered skeleton-cleavable hyperbranched polymer prodrug as unimolecular micelles for tumor-specific camptothecin delivery

Abstract

Prodrug unimolecular micelles based on dendrimers or hyperbranched polymers have attracted intense interest in tumor chemotherapy. The preparation of the former one is usually cumbersome, while the stable skeleton in the latter one restricts the drug release. Here, GSH-triggered skeleton-cleavable hyperbranched polymer prodrug was designed via a “Bottom-up” construction strategy, by the self-condensing vinyl polymerization (SCVP) of GSH-sensitive prodrug monomer MA-SS-CPT and PEGMA with a GSH-sensitive inimer MA-SS-Br. It could self-assemble into stable unimolecular micelles, possessing GSH-triggered drug release and disintegration of the hyperbranched skeleton. So, they showed an excellent tumor-specific CPT release in the in vitro drug release and consequently tumor-specific cytotoxicity with an enhanced tumor cell growth inhibition than the free CPT.