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Infection-adaptive regenerative wound healing through rationally engineered copper-polyphenol artificial enzymes

Ziyi Jia1, Lina Sun2, Liman Liu2

  • 1Affiliated Hospital of Shandong Second Medical University, Shandong Second Medical University, 261053, Shandong, PR China; School of Pharmacy, Shandong Second Medical University, Weifang 261053, Shandong, PR China.

Journal of Inorganic Biochemistry
|October 31, 2025
PubMed
Summary

A novel copper-based artificial enzyme, PRSA-Cu, combats bacterial infections by amplifying oxidative stress and depleting antioxidants. This multi-mechanism approach shows promise for wound healing by eradicating biofilms and stimulating tissue repair.

Keywords:
Artificial enzymeGSH-Px-likePOD-likePhototherapyPolyphenol coordination polymer

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Catalysis

Background:

  • Conventional artificial enzyme therapies for bacterial infections are limited by monofunctionality and low efficiency.
  • There is a need for advanced antimicrobial strategies that overcome bacterial resistance and enhance therapeutic outcomes.

Purpose of the Study:

  • To develop a multi-functional artificial enzyme, PRSA-Cu, with enhanced antibacterial properties.
  • To investigate the synergistic mechanisms of PRSA-Cu, including oxidative stress amplification, antioxidant depletion, photothermal enhancement, and oxygen-independent photodynamic activity.

Main Methods:

  • Development of PRSA-Cu, a copper-phenolic coordination polymer with multi-copper centers and mixed-valence states.
  • In vitro assessment of antibacterial activity against S. aureus and E. coli, including membrane integrity.
  • In vivo evaluation of wound healing efficacy, focusing on biofilm eradication and angiogenesis.

Main Results:

  • PRSA-Cu demonstrated synergistic antibacterial effects by generating hydroxyl radicals, depleting glutathione, and utilizing photothermal and photodynamic activities.
  • The artificial enzyme induced periplasmic membrane disintegration and cytoplasmic leakage in bacteria.
  • In vivo studies showed accelerated wound closure, biofilm eradication, and stimulated angiogenesis within 9 days.

Conclusions:

  • PRSA-Cu represents a significant advancement over monofunctional artificial enzymes, offering a multi-pathway approach for bacterial infection treatment.
  • The synergistic interplay of heat, radicals, and redox reactions provides a powerful self-amplifying antibacterial cycle.
  • This platform holds potential for clinical translation in treating complex bacterial infections and promoting wound healing.