In‐Situ Dynamic Chemical Reconstruction Synthesis of Dual‐Antioxidants for Pulmonary Arterial Hypertension Treatment

ABSTRACT Pulmonary arterial hypertension (PAH) is a serious circulatory system disease characterized by redox imbalance, which results from the overexpressed reactive oxygen species (ROS) and inactivated antioxidation defense system. In this work, a dynamic chemical reconstruction strategy has been developed for PAH treatment through the in situ synthesis of antioxidant nanocatalyst MoO y and selenium oxyanions from a molybdenum selenide nanosystem in response to the oxidative microenvironment of PAH. MoO y nanoparticles catalyze the exogenous antioxidation reactions to scavenge ROS efficiently, while the soluble selenium oxyanions upregulate the expression of selenoproteins to reinforce the endogenous antioxidant defense system. These two processes cooperatively alleviate oxidative stress of pulmonary artery smooth muscle cells (PASMCs), thus suppressing their malignant proliferation/migration and finally mitigating pulmonary arterial remodeling for PAH treatment. This work presents a dynamic chemical reconstruction strategy for in situ synthesis of exogenous and endogenous antioxidants, offering a dual‐axis antioxidation approach for the treatment of multiple redox imbalance‐associated diseases.