Atomic-engineered Ru single-atom-catalyst nanoplatforms with NIR-II-triggered oxidase-peroxidase cascades for bacterial pneumonia

<h2>Summary</h2> Multidrug-resistant bacterial pneumonia (MDR-BP), particularly involving biofilm eradication, presents therapeutic challenges. While reactive oxygen species (ROS)-mediated chemodynamic therapy offers antibacterial potential, limitations in biocatalytic performance and nanotherapeutic efficacy hinder traditional approaches. We developed nitrogen-doped ruthenium single-atom catalysts (Ru-N-SACs) as a dual-functional nanotherapeutic platform. This nanozyme exhibits peroxidase-mimicking catalytic activity, generating ROS selectively. Near-infrared laser stimulation further enhances its activity and provides photothermal disruption of biofilms. The resulting synergistic action achieves complete biofilm eradication and improves survival in pneumonia models. Comprehensive multi-omics analyses elucidated the therapeutic effectiveness and regulatory mechanisms of Ru-N-SACs against MDR-BP pathogenesis. This work demonstrates a paradigm combining catalytic ROS generation and photothermal therapy for managing deep-tissue infections. It advances the design of precision-engineered nanozymes within antimicrobial nanomedicine, addressing the critical need for innovative strategies against MDR pathogens.