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<p>Chronic obstructive pulmonary disease (COPD) is characterized by persistent oxidative stress and inflammation, for which current antioxidant therapies lack efficiency and targeting. Here, we developed macrophage membrane-biomimetic bimetallic manganese-platinum nanozymes (MM-BiMP NZs) for targeted pulmonary delivery. The synthesized MM-BiMP NZs retained potent scavenging activity against multiple reactive oxygen species (ROS), including hydroxyl radicals, singlet oxygen, and superoxide anions. Using an acute lipopolysaccharide-induced lung injury model, we determined 2.5&#xa0;mg/kg as a safe and effective dose for intratracheal administration. In a cigarette smoke-induced COPD mouse model, treatment with MM-BiMP NZs significantly attenuated pulmonary oxidative stress, reduced inflammatory cytokine levels, improved lung function, and ameliorated emphysema and airway remodeling. The <i>vitro</i> experiments demonstrated that MM-BiMP NZs were efficiently internalized, mitigated cigarette smoke extract-induced oxidative damage, and suppressed pro-inflammatory cytokine release both in the bronchial epithelial cells and alveolar macrophages. Mechanistically, transcriptomic and biochemical analyses revealed that the therapeutic effects of MM-BiMP NZs were mediated through the inhibition of the ROS-PI3K-AKT signaling pathway. This study presents a novel biomimetic nanoplatform that effectively targets the pulmonary microenvironment, combats oxidative stress, and alleviates experimental COPD, offering a promising strategy for this debilitating disease.</p> Graphical Abstract <p></p>

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Macrophage membrane-biomimetic bimetallic manganese-platinum nanozymes ameliorate intrapulmonary oxidative stress and inflammation in experimental COPD

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月14日

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  • Yuan Zhan,
  • Junhao Zhou,
  • Ruonan Yang,
  • Xinyue Duan,
  • Hao Li,
  • Chaoli Lai,
  • Yuanchun Li,
  • Li Xiao,
  • Linlin Huo,
  • Mi Zhang,
  • Shuliang Guo

摘要

Chronic obstructive pulmonary disease (COPD) is characterized by persistent oxidative stress and inflammation, for which current antioxidant therapies lack efficiency and targeting. Here, we developed macrophage membrane-biomimetic bimetallic manganese-platinum nanozymes (MM-BiMP NZs) for targeted pulmonary delivery. The synthesized MM-BiMP NZs retained potent scavenging activity against multiple reactive oxygen species (ROS), including hydroxyl radicals, singlet oxygen, and superoxide anions. Using an acute lipopolysaccharide-induced lung injury model, we determined 2.5 mg/kg as a safe and effective dose for intratracheal administration. In a cigarette smoke-induced COPD mouse model, treatment with MM-BiMP NZs significantly attenuated pulmonary oxidative stress, reduced inflammatory cytokine levels, improved lung function, and ameliorated emphysema and airway remodeling. The vitro experiments demonstrated that MM-BiMP NZs were efficiently internalized, mitigated cigarette smoke extract-induced oxidative damage, and suppressed pro-inflammatory cytokine release both in the bronchial epithelial cells and alveolar macrophages. Mechanistically, transcriptomic and biochemical analyses revealed that the therapeutic effects of MM-BiMP NZs were mediated through the inhibition of the ROS-PI3K-AKT signaling pathway. This study presents a novel biomimetic nanoplatform that effectively targets the pulmonary microenvironment, combats oxidative stress, and alleviates experimental COPD, offering a promising strategy for this debilitating disease.

Graphical Abstract