Multi-omics decodes a defect-interface dual-engineered PtPb@SbO3-x nanozyme for NIR-II photothermal-amplified eradication of drug-resistant pneumonia.

Managing pneumonia caused by multidrug-resistant (MDR) bacteria presents significant clinical challenges. The near-infrared II (NIR-II) laser irradiance exhibits strong photothermal conversion capabilities, making it a promising candidate for photothermal and chemodynamic therapies as non-antibiotic strategies. However, traditional methods are often hindered by issues such as the uncontrollable production of reactive oxygen species and the low efficiency associated with NIR-II photothermal therapy. This underscores the necessity for precisely regulated and highly effective synergistic therapies. To address these limitations, we have innovatively developed a defect/interface dual-engineered nanozyme (PtPb@SbO3-x) and comprehensively characterized its atomic-scale structure and catalytic mechanisms using density functional theory calculations and synchrotron radiation techniques. In vitro experiments demonstrated that PtPb@SbO3-x could efficiently eliminate drug-resistant bacteria and disrupt biofilm structures under low-concentration hydrogen peroxide and NIR-II irradiation while exhibiting excellent biocompatibility. In pneumonia models, the nanozyme enabled rapid infection clearance and significantly reduced inflammatory responses via synergistic photothermal and chemodynamic therapy effects. Furthermore, integrated multi-omics analyses-including metabolomics, transcriptomics, and proteomics-systematically uncovered the molecular mechanisms driving its therapeutic efficacy. This study successfully establishes a non-antibiotic nanozyme-based therapeutic strategy that is efficient, low in toxicity, and non-invasive for treating MDR bacterial infections. It also provides a solid theoretical basis and technical framework for the rational design of defect/interface dual-engineered nanoplatforms.