Ultrasound-Responsive Drug Delivery System Based on Piezoelectric Catalytic Mechanisms

Ultrasound-responsive nanomaterials represent a promising approach for achieving non-invasive and localized drug delivery within tumor microenvironments. In this study, we developed a piezocatalysis-assisted hydrogel system that integrates reactive oxygen species (ROS) generation with stimulus-responsive drug release. The platform combines piezoelectric barium titanate (BTO) nanoparticles with a ROS-sensitive hydrogel matrix, forming an ultrasound-activated dual-function therapeutic system. Upon ultrasound irradiation, the BTO nanoparticles generate ROS-predominantly hydroxyl radicals (^•OH) and singlet oxygen (¹O₂)-through the piezoelectric effect, which triggers hydrogel degradation and facilitates the controlled release of encapsulated therapeutic agents. The composition and kinetics of ROS generation were evaluated using radical scavenging assays and fluorescence probe techniques, while the drug release behavior was validated under simulated oxidative environments and acoustic fields. Structural and compositional characterizations (TEM, XRD, and XPS) confirmed the quality and stability of the nanoparticles, and cytocompatibility was assessed using 3T3 fibroblasts. This synergistic strategy, combining piezocatalytic ROS generation with hydrogel disintegration, demonstrates a feasible approach for designing responsive nanoplatforms in ultrasound-mediated drug delivery systems.