Endowing Centrosymmetric Oxides with Effective Piezoelectricity via Oxygen Vacancy Engineering and Single-Atom Anchoring for Multicatalytic Sono-Immunotherapy.

Due to piezopotential-driven energy band tilting and the promotion of charge carrier separation, sonopiezoelectric therapy (SPT) holds promise in overcoming the limitations of band structure. However, the dependence of the piezoelectric effect on noncentrosymmetric crystal structures severely restricts the range of material selection. Herein, the intrinsic centrosymmetry of indium oxide (In2O3) nanocrystals was broken through oxygen vacancy (OV) engineering and single-atom anchoring strategies, resulting in copper single-atom-anchored OV-rich In2O3-x (CuSA-In2O3-x) with effective piezoelectricity. Through sonopiezoelectric catalysis, CuSA-In2O3-x can generate diverse reactive oxygen species, oxygen, and carbon monoxide and consume lactic acid and glutathione. Meanwhile, CuSA-In2O3-x also exhibits multiple enzyme-like activities, including catalase, peroxidase, glutathione oxidase, and nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) oxidase mimicking. Benefiting from the synergistic effect of multicatalytic performance, CuSA-In2O3-x under ultrasonic irradiation effectively disrupts the redox and energy metabolic homeostasis of tumor cells, thereby inducing apoptosis and ferroptosis and initiating immunogenic cell death to enhance the immune response. CuSA-In2O3-x combined with ultrasound not only significantly inhibits tumor growth but also promotes dendritic cell maturation, CD8+ T-cell infiltration, and memory T-cell differentiation, thereby activating immune protection and preventing tumor recurrence. As a representative application of centrosymmetric oxides in SPT, this work will expand the selection of piezoelectric sonocatalysts and provide valuable insights into sono-immunotherapy.