Engineered Nanocatalyst‐Enabled Cheolesterol Depletion for Enhanced Tumor Piezocatalytic Therapy

The inadequate generation of reactive oxygen species (ROS) and metastasis of malignant tumors are critical factors that limit the efficacy of conventional sonodynamic therapy in cancer treatment. Herein, an engineered piezocatalyst: cholesterol oxidase (CHO)-loaded Pt-ZnO nanoparticles (Pt-ZnO/CHO) that can explosively generate large amounts of ROS and block the metastasis of tumor, is developed for improving piezocatalytic tumor therapy. In this process, Pt-ZnO can substantially generate ROS via initiating ultrasound (US)-triggered piezocatalytic reactions. In situ-grown Pt nanoparticles not only optimize piezocatalytic activities but also facilitate oxygen (O₂) production, thereby synergistically boosting ROS generation. Moreover, O₂ produced by Pt-ZnO can accelerate the depletion of excess cholesterol in tumor cells under CHO catalysis to disrupt the integrity of lipid rafts and inhibit the formation of lamellipodia, significantly suppressing the proliferation and metastasis of tumor cells. This strategy by promoting ROS generation and blocking the metastatic pathway of cancer cells offers a new idea for enhanced efficacy-oriented cancer therapeutic strategies.