Ultrasound-activated piezo-hot carriers trigger tandem catalysis coordinating cuproptosis-like bacterial death against implant infections

Abstract Implant-associated infections due to the formation of bacterial biofilms pose a serious threat in medical healthcare, which needs effective therapeutic methods. Here, we propose a multifunctional nanoreactor by spatiotemporal ultrasound-driven tandem catalysis to amplify the efficacy of sonodynamic and chemodynamic therapy. By combining piezoelectric barium titanate with polydopamine and copper, the ultrasound-activated piezo-hot carriers transfer easily to copper by polydopamine. It boosts reactive oxygen species production by piezoelectrics, and facilitates the interconversion between Cu2 + and Cu + to promote hydroxyl radical generation via Cu + -catalyzed chemodynamic reactions. Finally, the elevated reactive oxygen species cause bacterial membrane structure loosening and DNA damage. Transcriptomics and metabolomics analysis reveal that intracellular copper overload restricts the tricarboxylic acid cycle, promoting bacterial cuproptosis-like death. Therefore, the polyetherketoneketone scaffold engineered with the designed nanoreactor shows excellent antibacterial performance with ultrasound stimulation and promotes angiogenesis and osteogenesis on-demand in vivo.