Defect‐Engineering Bismuth‐Based Homologous Schottky Heterojunction for Metabolic Regulation‐Augmented Sonodynamic Tumor Therapy

Abstract Sonodynamic therapy demonstrates tremendous potential in biomedicine due to its non‐invasiveness, deep tissue penetration, and spatiotemporal controllability. However, the lack of favorable nanosonosensitizers with prominent reactive oxygen species generation capability and green chemical constituents remains a significant challenge for its broad biomedical applications. Herein, a homologous bismuth‐based nanosonosensitizer (Bi‐HJ) is designed and fabricated by direct defect engineering for combinational tumor therapy. Specifically, self‐derived Schottky heterojunction and oxygen vacancies are concurrently constructed in Bi‐HJ, which prominently promotes the separation of ultrasound‐triggered electron–hole pairs and improves the charge utilization efficiency. With the porous structure, Bi‐HJ is loaded with a metabolic regulation drug atovaquone to block the mitochondrial respiration for oxygen‐economized sonodynamic tumor suppression. The strong near‐infrared absorption of Bi‐HJ imparted by oxygen vacancies allows the implementation of photothermal therapy. Accordingly, Bi‐HJ rationally combines two therapeutic modalities and metabolic regulation function, as well as computed tomography imaging ability, thus achieving effective tumor theranostics in vitro and in vivo. Therefore, this study provides new insight into the fabrication of homologous nanosonosensitizers without the introduction of other constituents for synergistically enhanced tumor therapy.