Enzyme-Responsive COF-Based Thiol-Targeting Nanoinhibitor for Curing Bacterial Infections

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Antimicrobial Research

Background:

• Pathogen infections, particularly those with antibiotic-resistant microbes, present significant clinical challenges.
• The thioredoxin (Trx) system is a viable antimicrobial target in Gram-positive bacteria, but the glutathione (GSH) system in Gram-negative bacteria poses a limitation.
• Novel therapeutic strategies are needed to overcome existing antimicrobial resistance.

Purpose of the Study:

• To develop and evaluate a novel nanoinhibitor for synergistic antibacterial effects against both Gram-positive and Gram-negative bacteria.
• To investigate the potential of the nanoinhibitor for wound healing and its biocompatibility.
• To address the limitations of current antimicrobial therapies by targeting bacterial antioxidant systems.

Main Methods:

• Synthesis of an enzyme-responsive covalent organic framework (COF) coloaded with silver nanoparticles (AgNPs) and ebselen (EBS), termed Ag-TA-CON@EBS@PEG.
• Utilizing azoreductase-triggered dissociation of the COF for targeted release of EBS and Ag+ at infection sites.
• In vitro evaluation of bactericidal performance against Gram-positive and Gram-negative bacteria, cytotoxicity assays, and in vivo studies in mice for biocompatibility, anti-inflammatory effects, and wound healing.

Main Results:

• The synthesized nanoinhibitor (Ag-TA-CON@EBS@PEG) demonstrated excellent bactericidal efficacy against both Gram-positive and Gram-negative bacteria in vitro.
• The nanoinhibitor exhibited low toxicity towards normal cells.
• In vivo studies showed favorable biocompatibility, anti-inflammatory properties, and effective wound healing capabilities in a mouse model.

Conclusions:

• The developed thiol-targeting nanoinhibitor offers a promising strategy for synergistic antibacterial therapy.
• The intelligent drug delivery platform enhances therapeutic outcomes and wound healing.
• This approach provides a potential clinical solution for combating antibiotic-resistant infections.