Facile Synthesis of a Redox-Responsive Hyperbranched Polymer Prodrug as a Unimolecular Micelle for the Tumor-Selective Drug Delivery

Demicellization of the self-assembled multimolecular micelles upon dilution restricts their application as drug delivery systems (DDSs) for tumor treatment. Here, a redox-responsive hyperbranched polymer prodrug (HBPP) was designed with a high drug content of 62.0% as a unimolecular micelle for the tumor-selective drug delivery, via the facile self-condensing vinyl polymerization (SCVP) of redox-responsive doxorubicin-based prodrug monomer MA-SS-DOX and poly(ethylene glycol) methacrylate (PEGMA) with p-chloromethylstyrene (CMS) as an inimer. The unimolecular micelle could be easily obtained with a hydrodynamic diameter of 122 nm, showing excellent GSH-triggered drug release performance with a cumulative release of 60.9% within 85 h but a low premature drug leakage of 3.2%. The unimolecular micelle exhibited selective tumor growth inhibition on HepG2 cells but no obvious cytotoxicity on L02 cells.