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Microenvironment-triggered cascade metal-polyphenolic nanozyme for ROS/NO synergistic hyperglycemic wound healing.

Shuo Shi1, Yaru Han2, Jianxing Feng3

  • 1Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, 712100, Shaanxi, China; College of Food Science and Engineering, Northwest A&F University, Yangling, 712100, Shaanxi, China.

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|May 31, 2024
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Summary

A novel nanozymatic system effectively treats hyperglycemic wounds by consuming glucose, generating antimicrobial agents, and regulating the wound microenvironment for enhanced healing and safety.

Keywords:
AntibacterialGas therapyHyperglycemic wound healingNanozymeROS

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Wound Healing Research

Background:

  • Hyperglycemic patients experience prolonged wound healing and increased infection risk due to elevated glucose levels.
  • Targeting the specific wound microenvironment (WME) for precise and safe therapy in hyperglycemic wounds presents a significant challenge.
  • Existing treatments often struggle to address the complex interplay of factors in hyperglycemic wound healing.

Purpose of the Study:

  • To engineer a WME-activated, nanozymatic system for effective treatment of hyperglycemic wounds.
  • To develop a safe and biocompatible therapeutic agent utilizing generally recognized as safe (GRAS) compounds.
  • To investigate the synergistic disinfection and healing capabilities of the nanozymatic system in a hyperglycemic wound model.

Main Methods:

  • Fabrication of a smart nanozymatic system (L-Arg/GOx@TA-Fe, LGTF) integrating a metal-polyphenol nanozyme (tannic acid-Fe3+, TA-Fe) and glucose oxidase (GOx).
  • Evaluation of the system's ability to consume high glucose concentrations and generate reactive oxygen species (ROS) and nitric oxide (NO) in situ.
  • Assessment of glucose level reduction, pH modulation of the WME, and enhancement of nanozyme catalytic activity.
  • Investigation of the synergistic disinfection and wound healing effects of the LGTF system in hyperglycemic wound models.

Main Results:

  • The LGTF nanozymatic system effectively consumes high glucose levels in the wound microenvironment.
  • In situ generation of ROS and NO by the system demonstrated synergistic antimicrobial activity against hyperglycemia-induced wound infections.
  • Glucose consumption and gluconic acid production lowered wound glucose levels and reduced WME pH, enhancing therapeutic efficacy.
  • Low-dose LGTF exhibited significant synergistic disinfection and accelerated wound healing in hyperglycemic models.
  • The system demonstrated superior biosafety and beneficial WME regulating capacity.

Conclusions:

  • The engineered LGTF nanozymatic system offers a promising therapeutic strategy for hyperglycemic wounds.
  • Its GRAS composition ensures superior biosafety, making it a benign therapeutic agent.
  • The system's ability to synergistically disinfect and promote healing by modulating the WME highlights its potential in clinical applications.