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

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 (O-1(2)) 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-1 alpha) 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.