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<p>Fungal infections, particularly intractable cases such as fungal keratitis (FK) and skin wound infections, remain a pressing global health challenge, further exacerbated by rising antifungal resistance and treatment-associated cytotoxicity. Herein, we report a highly effective, non-antibiotic therapeutic strategy integrating reactive oxygen species (ROS) generation and cuproptosis via ZnO<sub>2</sub> cores wrapped with a TA-Cu metal-phenolic network shell (ZnCu@TA) to combat fungi. Upon anchoring to fungal cell walls, ZnCu@TA responds to acidic microenvironments by releasing H<sub>2</sub>O<sub>2</sub> and Zn<sup>2+</sup> from the ZnO<sub>2</sub> core, thereby creates a concentrated burst of ROS that directly damages the cell wall, while promoting copper uptake to induce cuproptosis through mitochondrial dysfunction, leading to effective eradication of <i>Candida albicans</i> and biofilm disruption. In models of FK and skin wound infection, ZnCu@TA significantly reduced pathogens and inflammation with no observed adverse effects, and demonstrated promising preservation of visual function. These findings highlight ZnCu@TA as a safe and effective antifungal nanoplatform for treating superficial fungal infections, offering potential for clinical translation.</p> Graphical abstract <p></p>

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Zinc peroxide-copper bimetallic nanozyme with self-activated ROS and cuproptosis for superficial antifungal therapy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月8日

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  • Fuyao Chen,
  • Yang Ye,
  • Yitao Yao,
  • Jian He,
  • Xiaoning Yu,
  • Renfang Zhang,
  • Hailaiti Ailifeire,
  • Chenqi Luo,
  • Ke Yao,
  • Xiajing Tang,
  • Xingchao Shentu

摘要

Fungal infections, particularly intractable cases such as fungal keratitis (FK) and skin wound infections, remain a pressing global health challenge, further exacerbated by rising antifungal resistance and treatment-associated cytotoxicity. Herein, we report a highly effective, non-antibiotic therapeutic strategy integrating reactive oxygen species (ROS) generation and cuproptosis via ZnO2 cores wrapped with a TA-Cu metal-phenolic network shell (ZnCu@TA) to combat fungi. Upon anchoring to fungal cell walls, ZnCu@TA responds to acidic microenvironments by releasing H2O2 and Zn2+ from the ZnO2 core, thereby creates a concentrated burst of ROS that directly damages the cell wall, while promoting copper uptake to induce cuproptosis through mitochondrial dysfunction, leading to effective eradication of Candida albicans and biofilm disruption. In models of FK and skin wound infection, ZnCu@TA significantly reduced pathogens and inflammation with no observed adverse effects, and demonstrated promising preservation of visual function. These findings highlight ZnCu@TA as a safe and effective antifungal nanoplatform for treating superficial fungal infections, offering potential for clinical translation.

Graphical abstract