Abstract

BP-Pt SA single-atom nanozyme enables NIR-II photothermal-amplified catalysis. • BP-Pt SA shows dual OXD/POD-like activities for efficient ROS generation. • Synergistic PTT/CDT eradicates MRSA, Streptococcus mutans and biofilms. • Deep abscess infection is cleared in vivo with accelerated tissue regeneration. Deep-seated bacterial infections remain difficult to eradicate owing to multidrug resistance, limited antibiotic penetration and the protective nature of biofilms. Here, we report a photothermally amplified nanozyme platform composed of platinum single atoms anchored on black phosphorus nanosheets (BP-Pt SA ) for non-antibiotic treatment of deep infections. Leveraging the deep tissue penetrability of the second near-infrared window, the hybrid material exhibits potent radiation capture and achieves a high photothermal conversion efficiency of 37.1% under 1064 nm irradiation, enabling effective heat generation in deep tissue. Simultaneously, atomically dispersed platinum endows BP-Pt SA with pronounced oxidase-like and peroxidase-like catalytic activities, which are further enhanced by photothermal heating to promote reactive oxygen species production. The combined photothermal and chemodynamic effects lead to efficient killing of methicillin-resistant Staphylococcus aureus and Streptococcus mutans , as well as robust disruption of established biofilms, at low material doses. Notably, serial passaging experiments demonstrate that BP-Pt SA  + NIR-II shows minimal propensity to induce resistance evolution compared with conventional antibiotic treatment. In a murine subcutaneous abscess model, BP-Pt SA activated by near-infrared irradiation eliminates deep bacterial infection, accelerates abscess resolution and promotes tissue regeneration without detectable systemic toxicity, with therapeutic efficacy superior to vancomycin. Transcriptomic analysis reveals simultaneous suppression of membrane integrity, energy transport and resistance-related pathways