Aqueous Self-Assembly of Block Copolymers to Form Manganese Oxide-Based Polymeric Vesicles for Tumor Microenvironment-Activated Drug Delivery
Yalei Miao, Yudian Qiu, Mengna Zhang, Ke Yan, Panke Zhang, Siyu Lu, Zhongyi Liu, Xiaojing Shi, Xubo Zhao
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 (PAA68–b–PEG86–b–PAA68)] in an aqueous phase, manganese oxide (MnO2) is first generated to drive phase separation of the PAA block to form the PAA68–b–PEG86–b–PAA68/MnO2 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 MnO2 to Mn2+ caused by endogenous glutathione (GSH) facilitates the disassembly of PAA68–b–PEG86–b–PAA68/MnO2 to enable its drug delivery at the tumor sites. The toxicity of DOX-loaded PAA68–b–PEG86–b–PAA68/MnO2 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.