Targeted MBene‐Based Photothermal Therapy With Active Host Thermoprotection for MRSA Keratitis

ABSTRACT Bacterial keratitis caused by methicillin‐resistant Staphylococcus aureus (MRSA) frequently results in severe corneal damage and visual impairment. Photothermal therapy (PTT) offers an antibacterial approach, but collateral heating limits its application to the ocular surface. Here, we engineered a fibronectin‐modified MBene nanoplatform (Fn@MB) that combines bacterial association, photothermal activity, and host‐cell protection. Fibronectin competition experiments supported receptor‐mediated MRSA binding, and finite‐element simulations predicted spatially confined thermal accumulation (SCTA) at the bacterial interface. Under 808 nm irradiation, Fn@MB achieved 99.85% bactericidal efficiency in vitro and disrupted mature biofilms. In thermally stressed corneal epithelial cells, Fn@MB was associated with integrin β1 clustering, FAK phosphorylation, increased HSF1/HSPA6/HSP70 expression, and cytoskeletal preservation, supporting a proposed host thermoprotection mechanism. Its intrinsic CAT‐, SOD‐, and GPx‐like activities also scavenged reactive oxygen species and reduced pro‐inflammatory cytokine expression. In a rat MRSA keratitis model, treatment reduced corneal bacterial burden and inflammation and promoted rapid re‐epithelialization and structurally sound stromal repair over 5 days. These findings support the preclinical potential of coupling targeted PTT with active host thermoprotection.