Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 61, Issue 3, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202112782
Keywords
carbon monoxide; MRSA infection; nitric oxide; photoresponsive; wound healing
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Funding
- National Key R&D Program of China [2020YFA0710700]
- National Natural Scientific Foundation of China (NNSFC) Projects [51690150, 51690154, 52021002, 52073270, U19A2094]
- Fundamental Research Funds for the Central Universities [WK2060190102]
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The covalent grafting of nitric oxide (NO) and carbon monoxide (CO) releasing moiety demonstrated superior antimicrobial effects on Gram-positive bacteria. Furthermore, this treatment showed better therapeutic capacity than vancomycin in a murine skin wound model.
The local delivery of gaseous signaling molecules (GSMs) has shown promising therapeutic potential. However, although GSMs have a subtle interplay in physiological and pathological conditions, the co-delivery of different GSMs for therapeutic purposes remains unexplored. Herein, we covalently graft a nitric oxide (NO)-releasing N-nitrosamine moiety onto the carbon monoxide (CO)-releasing 3-hydroxyflavone (3-HF) antenna, resulting in the first NO/CO-releasing donor. Under visible light irradiation, photo-mediated co-release of NO and CO reveals a superior antimicrobial effect toward Gram-positive bacteria with a combination index of 0.053. The synergy of NO and CO hyperpolarizes and permeabilizes bacterial membranes, which, however, shows negligible hemolysis and no evident toxicity toward normal mammalian cells. Moreover, the co-release of NO and CO can efficiently treat MRSA infection in a murine skin wound model, showing a better therapeutic capacity than vancomycin.
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