Near‐Infrared Light‐Activatable Dual‐Action Nanoparticle Combats the Established Biofilms of Methicillin‐Resistant Staphylococcus aureus and Its Accompanying Inflammation

Abstract Clinically, inhibition of both bacterial infection and excessive inflammation is a crucial step for improved wound treatments. Herein, the fabrication of near‐infrared‐light (NIR)‐activatable deoxyribonuclease (DNase)–carbon monoxide (CO)@mesoporous polydopamine nanoparticles (MPDA NPs) is demonstrated for efficient elimination of methicillin‐resistant Staphylococcus aureus (MRSA) biofilms and the following anti‐inflammatory activity. Specifically, thermosensitive CO‐gas‐releasing donors (CO releasing molecules, FeCO) are first encapsulated into MPDA NPs, followed by covalently immobilizing deoxyribonuclease I (DNase I) on the surfaces of MPDA NPs. DNase I can degrade the extracellular DNA in biofilms, which site specifically destroys the compactness of the biofilms. With NIR irradiation, DNase–CO@MPDA NPs display great photothermal ability, and further trigger on‐demand delivery of bactericidal CO gas that can adequately permeate the impaired biofilms. Eventually, they achieve effective MRSA biofilm elimination in virtue of the synergistic effects of both DNase I participation and CO‐gas‐potentiated photothermal therapy. Importantly, the inflammatory responses of DNase–CO@MPDA NPs and NIR‐treated wounds are simultaneously alleviated owing to the anti‐inflammatory features of released CO. Finally, NIR‐activatable DNase–CO@MPDA NPs accelerate the healing process of MRSA‐biofilm‐infected cutaneous wounds. Taken together, this phototherapeutic strategy displays great therapeutic potential in treating the formidable clinical problems caused by MRSA biofilms and the accompanying inflammation.