Facile synthesis of a hyperbranched polymer prodrug as unimolecular micelles for overcoming multidrug resistance

Unimolecular micelles have attracted more interest as drug delivery systems (DDSs) owing to their superior stability. Here, a hyperbranched polymer prodrug (HBPP) was designed with a high drug content of 57.6% as unimolecular micelles for enhanced intracellular drug delivery via self-condensing vinyl polymerization (SCVP) of the pH-responsive doxorubicin-based prodrug monomer MH-DOX and polyethylene glycol methacrylate (PEGMA) with p-chloromethylstyrene (CMS) as an inimer. It could easily form unimolecular micelles with a hydrodynamic diameter of about 130 nm. Enhanced intracellular pH-triggered drug release was achieved owing to the unique structure, with a cumulative release of 91.8% within 58.5 h due to an auto-acceleration effect but with a minimal premature drug leakage of 3.9%. The enhanced intracellular drug delivery performance endowed the proposed unimolecular micelles with good inhibition of tumor growth on DOX-resistant MCF-7 (MCF-7/ADR) cells, showing promising potential for overcoming multidrug resistance.