Preparation of Drug Carriers with Dual Redox-responsibility via Multicomponent Polymerization of Alkynes

Multicomponent polymerization (MCP) has the advantages of high reaction efficiency, mild reaction conditions, high atomic economy and facile operation, which is a new trend in constructing complex and functional polymers. In order to explore the application of MCP in the design of drug delivery carriers, in this work, a dual redox-responsive amphiphilic polymer containing diselenide bonds was synthesized based on copper-catalyzed MCP. Amphiphilic polymer and doxorubicin (DOX) were used to construct drug-loaded nano micelles through self-assembly in aqueous solution. The characterization of the micelles shows that the particle size is about 130 nm, and the critical micelle concentration (CMC) value is 0.23 mg/mL. Under normal physiological conditions, the nano micelles remain structurally stable. However, in a tumor environment containing reactive oxygen species (ROS) or glutathione (GSH), DOX is released from the nano drug-loaded micelles, and the cumulative release amount of DOX reaches 100%. The main reason for this result is that the diselenide bond in the polymer backbone is cleaved under redox conditions. It is found that nano drug-loaded micelles have better drug release performance in the GSH environment than those in the ROS environment. Studies have shown that the redox-responsive amphiphilic polymer is conveniently constructed through MCP, and the polymer exhibits specific degradation properties in the tumor microenvironment. This work provides a new idea for the development and design of intelligent nano drug-loaded micelles.