Photothermal Nano‐Immunotherapy Against Methicillin‐Resistant Staphylococcus aureus (MRSA) Biofilm Infections

Abstract Methicillin‐resistant Staphylococcus aureus (MRSA) biofilm infections are a prevalent type of biofilm‐associated infection with a poor prognosis and antibiotic resistance. The senescence of immune cells in the immune microenvironment contributes to biofilm formation. In this study, Ti₃C₂ MXene‐PVA nanosheets loaded with metformin (Met@TiC) are developed for the treatment of MRSA biofilm infections. Nanosheets utilize near‐infrared light to induce photothermal effects and provide direct bactericidal activity against biofilm structures. Met, which is known for its anti‐inflammatory and anti‐senescence properties, modulates immune responses by revitalizing the function of senescent macrophages within the biofilm microenvironment, thereby enhancing their phagocytic and biofilm‐eradicating capabilities. The efficacy of this nanoplatform both in vitro and in an MRSA biofilm infection mouse model, demonstrating its potential as a photothermal nanoimmunotherapy for combating MRSA biofilm infections is validated. In summary, the Met@TiC nanoplatform offers a significant alternative to clinical solutions for MRSA biofilm infections.