A Self-Oxygenating Nanozyme Cascade System for Drug-Resistant Bacterial Infected Diabetic Wound Healing
Ningning Wang1, Wenying Mu1, Irina A Kolesnik2
1School of Chemistry and Environmental Engineering, Changchun University of Science and Technology, 7186 Weixing Road, Changchun 130022, China.
ACS Applied Materials & Interfaces
|November 11, 2025
Summary
Copper-doped iron oxide nanozyme (CFO@PEG NPs) synergizes with hydrogen peroxide to create a trienzyme cascade, effectively regenerating chronic diabetic wounds by combating biofilms and hypoxia.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Regenerative Medicine
Background:
- Chronic diabetic wounds present significant challenges due to biofilm infections, antibiotic resistance, hypoxia, and inflammation.
- Current treatments often struggle to address these multifaceted issues effectively.
Purpose of the Study:
- To develop a novel copper-doped iron oxide nanozyme (CFO@PEG NPs) to create a trienzyme catalytic cascade for enhanced diabetic wound regeneration.
- To investigate the nanozyme's ability to combat biofilms, reduce hypoxia, and modulate inflammation in infected diabetic wounds.
Main Methods:
- Synthesized and characterized cubic CuFe2O4 nanostructures (CFO@PEG NPs) with peroxidase-, glutathione peroxidase-, and catalase-like activities.
- Evaluated the nanozyme's efficacy in eradicating methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Escherichia coli (MREA) biofilms in vitro.
- Assessed the in vivo wound healing acceleration in MRSA-infected diabetic wound models, analyzing mechanisms including ROS generation, oxygen production, and macrophage polarization.
Main Results:
- CFO@PEG NPs demonstrated significant antimicrobial activity, eradicating 99.9% of MRSA and MREA, and clearing 90% of biofilms in vitro.
- In vivo studies showed accelerated wound closure within 8 days, attributed to ROS-mediated bacterial disruption, oxygen generation alleviating hypoxia (reducing HIF-1α, increasing CD31 neovessels), and M1 to M2 macrophage polarization.
- The treatment achieved full wound closure without observable systemic toxicity.
Conclusions:
- The developed CFO@PEG NPs effectively address the complex challenges of chronic infected diabetic wounds through a synergistic trienzyme cascade.
- This nanozyme-based therapeutic strategy offers a promising new paradigm for treating multidimensionally challenging infected wound regeneration.
