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<p>Drug-resistant bacterium-infected wounds pose a serious clinical challenge, underscoring the need for therapeutic materials that respond to dynamic healing stages. Herein, we report a sequential multimodal platform embedding a self-adaptive IrPtCu nanozyme into a madecassoside-enriched hyaluronic acid hydrogel (HIPCM) for rapid bacterial eradication and accelerated wound healing. Leveraging trimetallic synergy and pH-adaptive reactive oxygen species (ROS) regulation, IrPtCu nanozyme exhibits strong oxidase, peroxidase, glutathione oxidase, and glutathione peroxidase-like activities, enabling efficient ROS generation and potent antibacterial performance. After disinfection, it switches to ROS scavenging through superoxide dismutase and catalase-like cascades, alleviating oxidative stress and cooperating with madecassoside to promote tissue repair. In a methicillin-resistant <i>Staphylococcus aureus</i> (<i>MRSA</i>)-infected mouse model, HIPCM demonstrates strong antibacterial efficacy, promotes M2 macrophage polarization and angiogenesis, and accelerates high-quality repair. Preclinical studies in Bama mini-pigs further confirm improved collagen deposition, hair follicle regeneration, and functional restoration. This work offers a comprehensive strategy integrating adaptive nanozymes and natural herbal medicines for treating drug-resistant wounds.</p>

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Self-adaptive nanozymes with enhanced multi-enzyme activities for sequential multimodal therapy of drug-resistant bacteria-infected wounds

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月28日

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  • Xiaoyong Zhang,
  • Hang Yu,
  • Kai Zhu,
  • Yao Xiao,
  • Yuxuan Gong,
  • Dandan Che,
  • Wanyi Chen,
  • Guoxing You,
  • Xiyun Yan,
  • Quan Wang,
  • Kelong Fan,
  • Hong Zhou,
  • Gan Chen

摘要

Drug-resistant bacterium-infected wounds pose a serious clinical challenge, underscoring the need for therapeutic materials that respond to dynamic healing stages. Herein, we report a sequential multimodal platform embedding a self-adaptive IrPtCu nanozyme into a madecassoside-enriched hyaluronic acid hydrogel (HIPCM) for rapid bacterial eradication and accelerated wound healing. Leveraging trimetallic synergy and pH-adaptive reactive oxygen species (ROS) regulation, IrPtCu nanozyme exhibits strong oxidase, peroxidase, glutathione oxidase, and glutathione peroxidase-like activities, enabling efficient ROS generation and potent antibacterial performance. After disinfection, it switches to ROS scavenging through superoxide dismutase and catalase-like cascades, alleviating oxidative stress and cooperating with madecassoside to promote tissue repair. In a methicillin-resistant Staphylococcus aureus (MRSA)-infected mouse model, HIPCM demonstrates strong antibacterial efficacy, promotes M2 macrophage polarization and angiogenesis, and accelerates high-quality repair. Preclinical studies in Bama mini-pigs further confirm improved collagen deposition, hair follicle regeneration, and functional restoration. This work offers a comprehensive strategy integrating adaptive nanozymes and natural herbal medicines for treating drug-resistant wounds.