期刊
ACS APPLIED MATERIALS & INTERFACES
卷 14, 期 34, 页码 38483-38496出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.2c08845
关键词
covalent organic framework; thiol-dependent system; antibacterial activity; enzyme response; nanoinhibitor
资金
- Jiangsu Key Laboratory of Biofunctional Materials
- Natural Science Foundation of Jiangsu Province [BE2020347, BK20220323]
- Jiangsu Engineering Research Center for Biomedical Function Materials, Jiangsu Collaborative Innovation Center of Bio-medical Functional Materials, and Jiangsu Key Laboratory of Biofunctional Materials
In this study, we developed a thiol-targeting nanoinhibitor based on an enzyme-responsive covalent organic framework, which was co-loaded with silver nanoparticles and ebselen, to achieve synergistic antibacterial effects. The nanoinhibitor showed excellent bactericidal performance for both Gram-positive and Gram-negative bacteria in vitro, and exhibited low toxicity to normal cells. Additionally, it demonstrated favorable biocompatibility, anti-inflammatory properties, and effective wound healing abilities in mice.
Pathogen infections impose severe challenges in clinical practice, especially for patients infected with antibiotic-resistant microbes. The thioredoxin (Trx) system in Gram-positive bacteria serves as an ideal antimicrobial target for novel medicine design due to the structural differences from corresponding system in mammals. However, a backup thiol-dependent antioxidant glutathione (GSH) system limits the effectiveness of drugs in many Gram-negative bacteria. Herein, we synthesize a thiol-targeting nanoinhibitor based on an enzyme-responsive covalent organic framework (COF) coloaded with silver nanoparticles (AgNPs) and ebselen (EBS) (Ag-TA-CON@EBS@PEG) to exert synergistic antibacterial effects. Since azoreductase can dissociate the enzyme-responsive COF, we adopt this strategy to achieve the accurate release of EBS and Ag+ at infection sites. Our research identifies that the functionalized nanoinhibitor shows excellent bactericidal performance for Gram-positive and Gram-negative bacteria in vitro and exhibits low toxicity to normal cells. Besides, the nanoinhibitor presents favorable biocompatibility, anti-inflammatory property, and effective wound healing ability in mice. This paper provides a promising clinical strategy for synergistic antibacterial therapy and enhanced wound healing properties via an optimized combination of the targeted nanomedicines with an intelligent drug conveying platform.
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