Red Light-Triggered Intracellular Carbon Monoxide Release Enables Selective Eradication of MRSA Infection
Jian Cheng1, Guihai Gan1, Zhiqiang Shen1
1CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Science at the Microscale, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, 230026, Anhui, China.
Angewandte Chemie (International Ed. in English)
|April 8, 2021
Summary
Researchers developed nonmetallic, light-activated carbon monoxide (CO)-releasing micelles. These micelles selectively kill Staphylococcus aureus, including MRSA, and promote wound healing, distinguishing them from metal-based CO releasers.
Area of Science:
- Biochemistry and Medicinal Chemistry
- Antimicrobial Research
- Nanotechnology
Background:
- Carbon monoxide (CO) is a crucial gaseous signaling molecule with diverse biological functions.
- Metal carbonyls are used as CO-releasing molecules but their broad-spectrum antimicrobial activity complicates understanding the role of CO versus the metal ion.
- Distinguishing the source of antimicrobial effects in CO-releasing molecules is essential for targeted therapeutic development.
Purpose of the Study:
- To develop novel, nonmetallic carbon monoxide (CO)-releasing agents.
- To investigate the selective antimicrobial activity and mechanism of action of these new agents.
- To evaluate the therapeutic potential of nonmetallic CO-releasing micelles in treating bacterial infections, specifically MRSA-infected wounds.
Main Methods:
- Synthesis of nonmetallic CO-releasing micelles based on 3-hydroxyflavone derivatives.
- Utilized a photooxygenation mechanism for red light-triggered CO release (650 nm).
- Assessed selective cellular uptake and bactericidal effects against Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria.
- Evaluated therapeutic efficacy in a methicillin-resistant S. aureus (MRSA)-infected wound healing model.
Main Results:
- Developed nonmetallic micelles capable of releasing CO upon red light irradiation.
- Demonstrated selective uptake and bactericidal activity of the micelles against S. aureus, but not E. coli.
- Showed that these CO-releasing micelles effectively eradicated MRSA in infected wounds and accelerated healing.
Conclusions:
- Nonmetallic, light-activated CO-releasing micelles offer a selective approach to combating bacterial infections.
- The bactericidal effect is attributed to the released CO, decoupled from potentially toxic metal ions.
- These findings highlight the potential of nonmetallic CO-releasing micelles as a novel therapeutic strategy for MRSA infections and wound management.
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