2D Piezoelectric BiVO4 Artificial Nanozyme with Adjustable Vanadium Vacancy for Ultrasound Enhanced Piezoelectric/Sonodynamic Therapy

Abstract Increasing the yield of reactive oxygen species (ROS) to enhance oxidative stress in cells is an eternal goal in cancer therapy. In this study, BiVO 4 artificial nanozyme is developed with adjustable vanadium vacancy for ultrasound (US) enhanced piezoelectric/sonodynamic therapy. Under US excitation, the vanadium vacancy‐rich BiVO 4 nanosheets (abbreviated V v ‐r BiVO 4 NSs) facilitate the generation of a large number of electrons to improve the ROS yield. Meanwhile, the mechanical strain imposed by US irradiation makes the V v ‐r BiVO 4 NSs display a typical piezoelectric response, which tilts the conduction band to be more negative and the valance band more positive than the redox potentials of O 2 /O 2 •− and H 2 O/·OH, boosting the efficiency of ROS generation. Both density functional theory calculations and experiments confirm that the introduction of cationic vacancy can improve the sonodynamic effect. As expected, V v ‐r BiVO 4 NSs have better peroxidase enzyme catalytic and glutathione depletion activities, resulting in increased intracellular oxidative stress. This triple amplification strategy of oxidative stress induced by US substantially inhibits the growth of cancer cells. The work may open an avenue to achieve a synergetic therapy by introducing cationic vacancy, broadening the biomedical use of piezoelectric materials.