Application of a Cascaded Nanozyme in Infected Wound Recovery of Diabetic Mice

ACS Biomater Sci Eng. 2022 Apr 11;8(4):1522-1531. doi: 10.1021/acsbiomaterials.1c01590. Epub 2022 Mar 11.

Abstract

The emergence of peroxidase (POD)-like nanozyme-derived catalytic therapy has provided a promising choice for reactive oxygen species (ROS)-mediated broad-spectrum antibacterials to replace antibiotics, but it still suffers from limitations of low therapeutic efficiency and unusual addition of unstable H2O2. Considering that the higher blood glucose in diabetic wounds provides much more numerous nutrients for bacterial growth, a cascade nanoenzymatic active material was developed by coating glucose oxidase (GOx) onto POD-like Fe2(MoO4)3 [Fe2(MoO4)3@GOx]. GOx could consume the nutrient of glucose to produce gluconic acid (weakly acidic) and H2O2, which could be subsequently converted into highly oxidative OH via the catalysis of POD-like Fe2(MoO4)3. Accordingly, the synergistic effect of starvation and ROS-mediated therapy showed significantly efficient antibacterial effect while avoiding the external addition of H2O2 that affects the stability and efficacy of the therapy system. Compared with the bactericidal rates of 46.2-59.404% of GOx or Fe2(MoO4)3 alone on extended-spectrum β-lactamases producing Escherichia coli and methicillin-resistant Staphylococcus aureus, those of the Fe2(MoO4)3@GOx group are 98.396 and 98.776%, respectively. Animal experiments showed that the as-synthesized Fe2(MoO4)3@GOx could much efficiently promote the recovery of infected wounds in type 2 diabetic mice while showing low cytotoxicity in vivo.

Keywords: Fe2(MoO4)3; antibacterials; glucose oxidase; starvation therapy; wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Diabetes Mellitus, Experimental* / drug therapy
  • Escherichia coli
  • Glucose Oxidase / pharmacology
  • Glucose Oxidase / therapeutic use
  • Hydrogen Peroxide / pharmacology
  • Methicillin-Resistant Staphylococcus aureus*
  • Mice
  • Reactive Oxygen Species / pharmacology

Substances

  • Anti-Bacterial Agents
  • Reactive Oxygen Species
  • Hydrogen Peroxide
  • Glucose Oxidase