Fabrication of pH- and Ultrasound-Responsive Polymeric Micelles: The Effect of Amphiphilic Block Copolymers with Different Hydrophilic/Hydrophobic Block Ratios for Self-Assembly and Controlled Drug Release

Stimuli-responsive polymeric vehicles can change their physical or chemical properties when exposed to internal or external triggers, enabling precise spatiotemporal control of drug release. Nevertheless, systematic research is lacking in preparing dual stimuli-responsive amphiphilic block copolymers with different hydrophilic/hydrophobic block ratios in forming self-assembled structures. Here, we synthesized two types of block copolymers consisting of the hydrophobic segments (i.e., pH-responsive 2-(diethylamino)ethyl methacrylate (DEA) and ultrasound-responsive 2-methoxyethyl methacrylate (MEMA)) and hydrophilic poly(ethylene glycol) methyl ether (mPEG) segments, forming mPEG_X-<i>b</i>-P(DEA_Y-<i>co</i>-MEMA_Z). These amphiphilic block copolymers can self-assemble to form polymeric micelles, and their structures (e.g., size) and properties (e.g., critical vesicle concentration, stability, stimuli-responsiveness to pH and ultrasound, drug loading efficiency, and controlled drug release performance) were thoroughly investigated. <i>In vitro</i> cell studies further demonstrate that ultrasound can efficiently trigger drug release from polymeric micelles, emphasizing their potential for controlled drug delivery in therapeutic applications.