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

• Published in: Angewandte Chemie International Edition Vol. 60; no. 24; pp. 13513 - 13520
• Main Authors: Cheng, Jian, Gan, Guihai, Shen, Zhiqiang, Gao, Lei, Zhang, Guoying, Hu, Jinming
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 07.06.2021; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: antibacterial agents; Antiinfectives and antibacterials; Antimicrobial activity; Carbon monoxide; Carbonyl compounds; Carbonyls; Chemistry; Chemistry, Multidisciplinary; Drug resistance; E coli; Gram-negative bacteria; Irradiation; Light irradiation; Metal carbonyls; Metals; Methicillin; Micelles; MRSA; photooxidation; Physical Sciences; Releasing; Science & Technology; Staphylococcus aureus; Transition metals; Wound healing; carbon monoxide; wound healing; photooxidation; antibacterial agents; MRSA
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202104024

Carbon monoxide (CO) is an important gaseous signaling molecule. The use of CO‐releasing molecules such as metal carbonyls enables the elucidation of the pleiotropic 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. Here, we develop nonmetallic CO‐releasing micelles via a photooxygenation mechanism of 3‐hydroxyflavone derivatives, enabling CO release under red light irradiation (e.g., 650 nm). Unlike metal carbonyls that non‐specifically internalize into both Gram‐positive and Gram‐negative bacteria, the nonmetallic micelles are selectively taken up by S. aureus instead of E. coli cells, exerting a selective bactericidal effect. Further, we demonstrate that the CO‐releasing micelles can cure methicillin‐resistant S. aureus (MRSA)‐infected wounds, simultaneously eradicating MRSA pathogens and accelerating wound healing. Metal‐free CO‐releasing micelles can be selectively taken up by Gram‐positive bacteria, exerting a narrow‐spectrum bactericidal activity toward only Gram‐positive bacteria under red light irradiation. The CO‐releasing micelles synergistically eradicate MRSA pathogens and accelerate MRSA‐infected wound healing.