Aqueous Self-Assembly of Block Copolymers to Form Manganese Oxide-Based Polymeric Vesicles for Tumor Microenvironment-Activated Drug Delivery

AbstractSection Highlights The formation of manganese oxide induces self-assembly of block copolymers to form polymeric vesicles. The polymeric vesicles possessed strong stability and high drug loading capacity. The drug-loaded polymeric vesicles have been demonstrated, especially in in vivo studies, to exhibit a higher efficacy of tumor suppression without known cardiotoxicity. AbstractSection Abstract Molecular self-assembly is crucially fundamental to nature. However, the aqueous self-assembly of polymers is still a challenge. To achieve self-assembly of block copolymers [(polyacrylic acid– block –polyethylene glycol– block –polyacrylic acid (PAA 68 – b –PEG 86 – b –PAA 68 )] in an aqueous phase, manganese oxide (MnO 2 ) is first generated to drive phase separation of the PAA block to form the PAA 68 – b –PEG 86 – b –PAA 68 /MnO 2 polymeric assembly that exhibits a stable structure in a physiological medium. The polymeric assembly exhibits vesicular morphology with a diameter of approximately 30 nm and high doxorubicin (DOX) loading capacity of approximately 94%. The transformation from MnO 2 to Mn 2+ caused by endogenous glutathione (GSH) facilitates the disassembly of PAA 68 – b –PEG 86 – b –PAA 68 /MnO 2 to enable its drug delivery at the tumor sites. The toxicity of DOX-loaded PAA 68 – b –PEG 86 – b –PAA 68 /MnO 2 to tumor cells has been verified in vitro and in vivo. Notably, drug-loaded polymeric vesicles have been demonstrated, especially in in vivo studies, to overcome the cardiotoxicity of DOX. We expect this work to encourage the potential application of polymer self-assembly.