Defect-engineered PdOv-TiOX nanozymes with NIR-II responsiveness for synergistic photothermal–chemodynamic therapy of drug-resistant bacterial infections

Traditional treatments for drug-resistant bacterial keratitis and pneumonia often prove ineffective due to the presence of biofilm barriers and multidrug resistance. Existing nano-antibacterial systems face several limitations, including insufficient tissue penetration depth in the first near-infrared (NIR I) window, the inability of a single treatment modality to simultaneously disrupt biofilms and eradicate residual bacteria, and a lack of efficacy validation in cross-organ (ocular-pulmonary) infection models. In this study, we employed a defect engineering strategy, to construct a palladium-doped TiO 2 nanozyme with oxygen vacancies (PdO V -TiO X ). This nanozyme achieves multiple antibacterial effects through the synergistic combination of second near-infrared (NIR-II) laser-activated photothermal therapy and chemodynamic therapy. Under 1064 nm laser excitation, the system utilizes oxygen vacancy-enhanced peroxidase-like activity to continuously generate hydroxyl radicals (•OH), resulting in a 5.2-fold increase in radical production compared to dark conditions. Additionally, it induces a local temperature rise (ΔT = 28.2 °C). These combined effects—physical disruption of the biofilm matrix and ROS-mediated oxidative stress—effectively dismantle the defense mechanisms of drug-resistant bacteria. In models of drug-resistant Staphylococcus aureus keratitis and pneumonia, PdO V -TiO X demonstrated therapeutic efficacy in both the eye and lung, indicating the broad cross-organ applicability of this treatment. Under NIR-II irradiation, the PdO V -TiO X nanozyme significantly elevated ROS levels at the infection site, achieving efficient bactericidal action while effectively penetrating and disrupting mature biofilms. This work presents a novel defect-engineering-regulated nanozyme synergistic therapeutic strategy for the treatment of multidrug-resistant bacterial infections.