PtCu Nanosonosensitizers with Inflammatory Microenvironment Regulation for Enhanced Sonodynamic Bacterial Elimination and Tissue Repair

Abstract Sonodynamic therapy (SDT) is considered a reliable replacement therapy to overcome the resistance to antibiotics and the limited tissue penetration of traditional photo‐induced therapy. Herein, ultrasmall platinum‐copper alloy nanoparticles (PtCu NPs) modified with poly (maleic anhydridealt‐1‐octadecene)‐polyethylene glycol (C₁₈PMH‐PEG) with high sonodynamic activity, strong catalytic ability, and good glutathione (GSH) depletion performance are synthesized for highly efficient bacterial elimination. PtCu NPs obtained through a thermal decomposition approach can generate high toxic singlet oxygen (¹O₂) under ultrasound (US) irradiation, showing good sonodynamic performance. Meanwhile, the partial oxygenation formed on the surface of PtCu NPs endows them with good Fenton‐like catalytic performance and superior GSH‐depleting ability, thus enhancing reactive oxygen species (ROS) generation. In vitro experiments confirm that the synthesized PtCu‐ NPs can not only efficiently kill both gram‐positive and gram‐negative bacteria but also eliminate staphylococcus aureus (S. aureus) infection through ROS generation and then accelerate wound healing in the S. aureus‐infected wound model. Meanwhile, the copper ions released from PtCu NPs can promote cell migration and angiogenesis through the up‐regulation of hypoxia inducible factor (HIF‐1α) and platelet endothelial cell adhesion molecule (CD31). Finally, the S. aureus‐induced deep‐seated osteomyelitis infection and bone destruction were successfully inhibited by the PtCu‐mediated combination therapy. Our work highlights a novel SDT strategy for enhanced sonodynamic bacteria elimination and tissue repair.