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

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.