Engineering 2D Bi4NbO8Br single crystalline nanosheets for piezoelectric and piezodynamic tumor nanotherapy

Piezoelectric biomaterials with mechanical–electrical energy conversion characteristic and reactive oxygen species (ROS) generation feature have become an emerging therapeutic platform with high therapeutic specificity and efficacy. In this work, 2D layered Bi4NbO8Br (BNB) single crystalline nanosheets with exceptional piezoelectric properties are rationally designed and engineered for ultrasound (US)-triggered piezodynamic hepatocarcinoma treatment. Under US excitation, the mechanical strain of 2D layered BNB nanosheets causes piezoelectric polarization and band tilting, favoring incremental ROS production. The as-synthesized BNB nanosheets enable mitochondrial damage of cancer cells by the regulation of the phosphorylation of the MAPK pathway. In vitro cellular level assessments and in vivo antineoplastic results demonstrated that the engineered 2D layered single crystalline nanosheets with US irradiation substantially inhibited the growth of hepatocellular carcinoma. This work expands the category of 2D piezoelectric biomaterials and opens up a new direction to explore exogenous US-activated piezodynamic strategies for efficient tumor treatment.