A Sonopiezoelectric Z-Scheme Nanoplatform Synergizing Trace Ag ⁺ for Eradicating Methicillin-Resistant <i>Staphylococcus aureus</i> -Induced Pneumonia

The underlying mechanisms by which heterogeneous interfaces enhance piezoelectric catalytic effects under ultrasonic irradiation, along with their potential biomedical applications, remain poorly understood. In this study, a versatile Z-Scheme nanoplatform by encapsulating the BiO_2-x/Ag₃PO₄ heterojunction within poly(lactic-<i>co</i>-glycolic acid) (PLGA) microspheres (BA@PLGA) was developed for ultrasound-activated deep-lung antibacterial therapy. The Z-scheme heterojunction synergistically integrates piezoelectric and built-in electric fields, achieving 2.2 and 4.7-fold enhancements in piezoelectric (<i>d</i>₃₃) and electromechanical coupling (<i>k</i>) coefficients, respectively. Ultrasonic-induced dynamic modulation of the piezoelectric potential in BiO_2-x/Ag₃PO₄ generated a "carrier-pumping" effect, which enhanced polarized charge migration efficiency and thereby markedly amplified reactive oxygen species (ROS) production. Consequently, with the assistance of trace Ag⁺, 99.87 ± 0.05% of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) were effectively eradicated within 15 min <i>in vitro</i>. Prokaryotic transcriptome analysis further revealed that the synergistic effect of ROS and trace Ag⁺ disrupted the cell envelope and interfered with the core metabolic pathways of MRSA. This ultrasound-activated platform, integrating piezocatalysis and trace Ag⁺, achieved over 99.9% bacterial clearance rapidly (1.6log superiority over gentamicin) and alleviated inflammation in a MRSA-induced pneumonia, demonstrating considerable potential for combating bacterial infections in deep-seated tissues.