Fabrication of Dual-Redox Responsive Supramolecular Copolymers Using a Reducible β-Cyclodextran-Ferrocene Double-Head Unit.

Self-assembly of amphiphilic block copolymers into well-defined nanostructures as drug delivery systems for the treatment of cancer has been a hot subject of research. However, sequential polymerizations synthesized amphiphilic block copolymers with covalent links suffered mainly from multistep synthesis and purification procedures as well as repeated optimization of polymer composition to form aggregates with well-defined structures. To overcome these drawbacks, supramolecular amphiphilic block copolymers with noncovalent links were developed to provide simplicity as required. Herein, we designed and prepared a reducible β-cyclodextran (β-CD)-ferrocene (Fc) double-head unit from which a dual-redox responsive supramolecular amphiphilic copolymer was fabricated together with a traditional polymer block through supramolecular induced polymerization. Typically, well-defined supramolecular micelles and vesicles were fabricated, respectively. Due to the integration of oxidation-sensitive noncovalent β-CD/Fc connections and reduction-sensitive covalent disulfide bridges in the polymer backbone, the resulting supramolecular micelles and vesicles showed structural deformation and accelerated drug release in response to both intracellular reducing and oxidizing environments, thus, presenting a new platform for both reactive oxygen species (ROS) and glutathione (GSH)-triggered anticancer drug delivery.