Red Light-Triggered Intracellular Carbon Monoxide Release Enables Selective Eradication of MRSA Infection.

Carbon monoxide (CO) has been known as an important gaseous signaling molecule. The use of CO-releasing molecules (CORMs) such as metal carbonyls offers the possibility to elucidate the pleiotropic physiological functions of CO. Although metal carbonyls show a broad-spectrum antimicrobial activity, it remains unclear whether the bactericidal property originates from the transition metals or the released CO. Herein, we develop nonmetallic micellar nanoparticles for localized CO delivery via a photooxygenation mechanism of 3-hydroxyflavone derivatives, enabling CO release under red light irradiation (e.g., 650 nm). In sharp contrast to metal carbonyls that non-specifically internalize into both Gram-positive and Gram-negative bacteria and show a broad-spectrum antibacterial activity, the nonmetallic micelles were selectively taken up by Staphylococcus aureus ( S. aureus ) instead of Escherichia coli ( E. coil ) cells, exerting a selective bactericidal effect toward S. aureus . Further, we demonstrate that the metal-free micelles can cure methicillin-resistant S. aureus (MRSA)-infected wounds in a full-thickness skin wound model by taking advantage of the localized release CO, simultaneously eradicating MRSA pathogens and accelerating wound healing.