Polyphenol-Regulated Bimetallic Artificial Metalloproteinases with Broad-Spectrum RONS Scavenging Activities for Diabetic Wound Repair

Abstract

Although numerous enzyme-mimicking nanomaterials have been developed to regulate the highly reactive oxygen species (ROS)-rich microenvironment of diabetic wounds for improving its healing, the poor broad-spectrum ROS-scavenging capacity and biological toxicity resulting from side reactions of nanomaterials still require improvement. To tackle these challenges, a polyphenol-mediated copper-bismuth bimetallic artificial metalloproteinases, CuBi-TA@BSA, based on a protein-scaffold design strategy, is conceptually engineered. The Bi and polyphenols can cooperatively enhance the loading capacity of Cu ions and regulate their coordination microenvironment within the BSA scaffold. The CuBi-TA@BSA exhibits remarkable scavenging activity against various ROS via effectively donating electrons, as well as the reaction pathway specificity of catalytic H₂O₂ decomposition without POD-like activity. Moreover, in vitro and in vivo studies further confirm that the CuBi-TA@BSA can protect cells from oxidative damage, inhibit the onset and progression of inflammation, and promote diabetic wound healing. This work presents a simple strategy for biocatalysts to effectively scavenge ROS and accelerate the diabetic wound-healing process, also provides a strategy for designing artificial metalloproteinases for antioxidative therapy.