Photothermal Nano‐Immunotherapy Against Methicillin‐Resistant <i>Staphylococcus aureus</i> (MRSA) Biofilm Infections

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.