Phytochemical nanozymes reprogram redox for balanced antimicrobial and regenerative therapy in acute and chronic

Yipeng Pang1, Fructueux Modeste Amona2, Xiaohan Chen2

  • 1Institute of Cellular and Molecular Biology, School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu, China; Department of Biophysics, School of Life Sciences, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.

Redox Biology
|June 13, 2025
PubMed

Insights

Phytochemical nanozymes combining ferulic acid and cerium oxide nanoparticles precisely balance antimicrobial action and tissue regeneration for chronic diabetic wounds. This novel approach effectively reduces oxidative stress and promotes healing.

Area of Science:

  • Biomaterials Science
  • Nanomedicine
  • Wound Healing Research

Background:

  • Chronic diabetic wounds suffer from oxidative stress and infection, hindering healing.
  • Elevated reactive oxygen species (ROS) have dual effects: bactericidal but also damaging to tissue regeneration.
  • Precise redox modulation is essential to balance antimicrobial and regenerative therapies.

Purpose of the Study:

  • To develop a phytochemical nanozyme system for precise redox modulation in wound therapy.
  • To integrate ferulic acid (FA) with cerium oxide nanoparticles (CeO2) for dual antimicrobial and regenerative effects.
  • To evaluate the efficacy of FA-CeO2 nanozymes in balancing antibacterial action and tissue repair.

Main Methods:

  • Fabrication and structural analysis of ferulic acid-cerium oxide (FA-CeO2) nanozymes.
  • Assessment of antioxidant activity via Ce3+/Ce4+ cycling and radical scavenging.
  • Evaluation of antimicrobial efficacy against S. aureus and E. coli.
  • In vitro studies on Nrf2/HO-1 pathway activation, cell proliferation, and collagen deposition.
  • In vivo testing in acute and diabetic wound models for wound closure and tissue regeneration.

Main Results:

  • FA-CeO2 nanozymes demonstrated uniform dispersion and pH-responsive release.
  • Potent antioxidant and radical scavenging activities were observed, mitigating oxidative stress.
  • Effective bacterial clearance against S. aureus and E. coli was achieved.
  • Enhanced Nrf2/HO-1 pathway activation and upregulated VEGF/CD31 expression promoted cell proliferation and collagen synthesis.
  • FA-CeO2 significantly accelerated wound closure, reduced bacterial load, and improved tissue regeneration in vivo with good biocompatibility.

Conclusions:

  • Phytochemical nanozymes offer precise redox modulation for effective wound therapy.
  • FA-CeO2 nanozymes successfully balance antimicrobial efficacy with tissue regeneration.
  • This dual-modality platform advances nanomedicine strategies for treating oxidative stress and promoting tissue repair in chronic wounds.