Redox-Responsive Cross-Linking of Polycarbonate Nanomedicines for Enhanced Stability and Controlled Drug Delivery

Self-assembled polymeric micelles formed from amphiphilic block copolymers offer a promising strategy for enhanced drug delivery due to their biocompatibility and controlled release. However, challenges such as their poor colloidal stability under diluted conditions and degradation during storage and circulation limit their further applications. To address these issues, we developed a straightforward method for constructing cross-linked polycarbonate micelles that enhance stability while allowing for controlled stimuli-responsive drug delivery. By utilizing disulfide-based cross-linking and covalent conjugation of the anticancer drug, our approach maintains micelle integrity and extremely high drug loading over extended periods as well as the superior control of triggered drug release compared to non-cross-linked versions, demonstrating enhanced stability in complex biological environments and improved anticancer efficacy, presenting a novel platform for stable polymer-drug conjugate nanocarriers, holding significant therapeutic potential for targeted cancer treatment.