Ultrasound‐Activated Piezocatalyst Triggers Sulfate Radical Production for Augmented Oxidative Tumor Suppression

Sonopiezoelectric therapy (SPT) has gained ever‐increasing prominence in tumor therapy as a combination of ultrasound (US) and piezoelectric nanomaterials to generate cytotoxic reactive oxygen species (ROS) for tumor suppression. In this study, the facile hydrothermal method is used to construct the distinct 2D piezocatalyst Bi 2 Fe 4 O 9 nanosheets (BFO NSs). The engineered BFO NSs can create a piezoelectric field when exposed to US irradiation, facilitating the separation of electron–hole (e − –h + ) pairs to play a crucial role in Fe 3+ /Fe 2+ circulation, which catalyzes the activation of peroxymonosulfate (PMS), resulting in an amplified production of cytotoxic sulfate radical (SO 4 •− ). The produced SO 4 •− combines with ROS generated by SPT including hydroxyl radicals (•OH), and singlet oxygen ( 1 O 2 ), leading to the augmented oxidative tumor suppression. The BFO NSs and PMS are further integrated into a thermal hydrogel (BFO/PMS‐Gel) for in vitro and in vivo investigations on their catalytic antitumor effects. In both in vitro and in vivo studies, it is validated that BFO/PMS‐Gel, under US irradiation, significantly enhances radicals generation efficiency, which achieves superior antitumor performance while maintaining high therapeutic biocompatibility and biosafety, providing a representative paradigm of US‐activated multiple radicals production as enabled by piezoelectric nanomedicine for antitumor treatment.