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 (Bi2O3@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 Bi2O3@AuBi (BAB) bimetallic nanozyme and modifying its surface with a bacterial-targeting ligand 4-mercaptophenylboronic acid (4-MPBA). Under US irradiation, Bi2O3 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.