Enhancing diabetic wound healing with a pH-responsive nanozyme hydrogel featuring multi-enzyme-like activities and oxygen self-supply

• Published in: Journal of controlled release 2024-01, Vol.365, p.905-918
• Main Authors: Li, Qiulan, Dong, Miaodan, Han, Qinqin, Zhang, Yijing, Yang, Dezhi, Wei, Daqiao, Yang, Yaling
• Format: Article
• Language: English
• ISSN: 0168-3659; 1873-4995; 1873-4995
• DOI: 10.1016/j.jconrel.2023.12.015

Diabetic wound treating remains a challenging due to bacterial infections, oxidative stress, tissue hypoxia, and high glucose levels. Herein, a multi-enzyme-like activities nanocomposite (Mo,Fe/Cu,I-Ag@GOx) was designed and anchored to a multifunctional fluorescence hydrogel. The nanozyme gel, loaded with glucose-oxidase (GOx), exhibits intrinsic GOx, peroxidase (POD)-, oxidase (OXD)-, catalase (CAT)- and superoxide dismutase (SOD)-like activities with pH-switchable glucose-initiated cascade reaction for diabetic wound healing. In the first cascade-reaction, initiated by GOx, the nanozyme gel catalyzes glucose and O into gluconic acid and H O to further generate superoxide anion radical (O ) and hydroxyl radicals (·OH) to eradicate bacteria. In the second cascade-reaction, as the wound pH changes alkalescent microenvironment, the nanozyme gel simulates SOD to transform O into O and H O , and then decomposes endogenous and exogenous H O into O via CAT-like activity to reduce oxidative stress and alleviate hypoxia. The gel by calcium ion (Ca ) cross-linked sodium alginate (SA) and chitosan (CS) containing nanozyme was constructed with injectability, adhesion and fluorescence properties, as well as beneficial biocompatible. Importantly, the water/alcohol solubility of the nanozyme gel allows it to be used as a dressing without causing secondary injury to the wound. The multifunctional fluorescence hydrogel exhibits efficiently promote pro-angiogenesis and bacteria-infected wound healing.