Oxygen‐Vacancy‐Rich Piezoelectric BiO_2−x Nanosheets for Augmented Piezocatalytic, Sonothermal, and Enzymatic Therapies

Abstract Piezocatalytic therapy is a new‐emerging reactive oxygen species (ROS)‐enabled therapeutic strategy that relies on built‐in electric field and energy‐band bending of piezoelectric materials activated by ultrasound (US) irradiation. Despite becoming a hot topic, material development and mechanism exploration are still underway. Herein, as‐synthesized oxygen‐vacancy‐rich BiO_2−x nanosheets (NSs) demonstrate outstanding piezoelectric properties. Under US, a piezo‐potential of 0.25 V for BiO_2−x NSs is sufficient to tilt the conduction band to be more negative than the redox potentials of O₂/^•O₂⁻, ^•O₂⁻/H₂O₂, and H₂O₂/^•OH, which initiates a cascade reaction for ROS generation. Moreover, the BiO_2−x NSs exhibit peroxidase and oxidase‐like activities to augment ROS production, especially in the H₂O₂‐overexpressed tumor microenvironment. Density functional theory calculations show that the generated oxygen vacancies in BiO_2−x NSs are favorable for H₂O₂ adsorption and increasing the carrier density to produce ROS. Furthermore, the quick movement of electrons enables an excellent sonothermal effect, for example, rapid rise in temperature to nearly 65 °C upon US with low power (1.2 W cm⁻²) and short time (96 s). Therefore, this system realizes a multimode synergistic combination of piezocatalytic, enzymatic, and sonothermal therapies, providing a new direction for defect engineering‐optimized piezoelectric materials for tumor therapy.