Citation: Wenjing Zhang, Yu Chen, Kun Xie, Rachel A. Jun, Run Wang, Ning Wang, Yingwei Li, Yongbo Song. Multifunctional hydrogel embedded with Au−Cu nanoclusters for catalytic cascade therapy of infected diabetic wounds[J]. Chinese Chemical Letters, ;2026, 37(9): 111481. doi: 10.1016/j.cclet.2025.111481 shu

Multifunctional hydrogel embedded with Au−Cu nanoclusters for catalytic cascade therapy of infected diabetic wounds

Wenjing Zhang ^{a, b, 1} ,
Yu Chen ^{b, 1} ,
Kun Xie ^b ,
Rachel A. Jun ^c ,
Run Wang ^d ,
Ning Wang ^b ,
Yingwei Li ^{c, *,} ,
Yongbo Song ^{a, b, *,}

a.
School of Pharmaceutical Sciences, Anhui Medical University, Hefei 230032, China
b.
School of Biomedical Engineering, Anhui Medical University, Hefei 230032, China
c.
Department of Chemistry, University of Hawai’i at Manoa, Honolulu, HI 96822, United States
d.
College & Hospital of Stomatology, Anhui Medical University, Hefei 230022, China

yingweil@hawaii.edu

ybsong860@ahmu.edu.cn

Received Date: 15 May 2025
Revised Date: 15 June 2025
Accepted Date: 17 June 2025
Available Online: 17 June 2025

Figures(6)

Diabetic wound healing is hindered by multidrug-resistant bacteria, hyperglycemia, and oxidative stress, making bacterial control and microenvironment modulation crucial. However, an all-in-one strategy is still under development. We report a cascade catalytic hydrogel by incorporating quantum-sized Au−Cu bimetallic nanoclusters with dual enzyme-mimetic activities and glucose oxidase into a cross-linked matrix of oxidized chondroitin sulfate and carboxymethyl chitosan. Three objectives are achieved in this system: (1) Utilizing glucose oxidase to decrease blood glucose levels while generating H₂O₂. (2) Producing hydroxyl radicals via peroxidase-like activity of Au−Cu nanoclusters, while simultaneously functioning as a glutathione peroxidase-like to deplete GSH levels, thereby achieving effective antibacterial effect. (3) The Schiff base bonds (-CH=N-) within the hydrogel will responsively cleavage under slightly acidic environment of wound to release the oxidized chondroitin sulfate, which is benefit for down-regulating the levels of inflammatory factors (TNF-α and IL-6), ultimately achieving an anti-inflammatory effect. Comprehensive in vitro and in vivo evaluations, including antibacterial testing, biocompatibility, rapid hemostasis (within 7 min), and 16S rRNA gene sequencing, revealed that the hydrogel effectively restored microbial diversity and rectified the disrupted wound microenvironment. This work established the Au−Cu/GOx-integrated hydrogel as a promising therapeutic platform for treating infected diabetic wounds and highlights the potential of Au–Cu nanoclusters in clinical application.
- Diabetic wound infection,
- Au−Cu nanoclusters,
- Injectable hydrogel,
- Catalytic cascade reactions,
- POD-like activity
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