A Solution to Nanozyme Inefficiency: Ultrasound‐Enhanced and Biofilm‐Targeted Catalytic Therapy for Eradicating Bacterial Infections

The inherent limitations of conventional nanozymes, particularly their suboptimal catalytic activity, severely restrict their efficacy against resilient bacterial biofilms. In response, an Au‐Bi bimetallic nanozyme‐based sonosensitizer (Bi 2 O 3 @AuBi‐arg/4‐MPBA, BABa4), which harnesses ultrasound (US) to power a multi‐modal antibacterial strategy, is engineered. The platform is constructed by loading the NO donor L‐arginine (L‐arg) onto a mesoporous Bi 2 O 3 @AuBi (BAB) bimetallic nanozyme and modifying its surface with a bacterial‐targeting ligand 4‐mercaptophenylboronic acid (4‐MPBA). Under US irradiation, Bi 2 O 3 acts as an efficient sonosensitizer, generating electron‐hole pairs, which not only produce singlet oxygen but also transfer to the AuBi nanozyme, markedly enhancing its POD‐like activity and creating a synergistic ROS storm. Concurrently, the US‐triggered release of nitric oxide from L‐arg degrades the extracellular polymeric substance (EPS) of biofilms by regulating cyclic dimeric guanosine monophosphate (c‐di‐GMP) levels. This multifaceted approach, combining sonodynamic therapy, US‐enhanced nanozyme catalysis, and NO‐mediated biofilm dispersion, demonstrates potent antibacterial activity and promotes effective wound healing, presenting a robust strategy for combating resistant bacterial infections.