Ultrasmall PtIr Bimetallic Nanozyme Treats Myocardial Infarction via Ischemic/Inflammatory Cardiac Microenvironment Remodeling

作者：Yuxuan Gong, Yao Xiao, Caiyan Zhao, Hongzhang Deng, Huaying Liu, Shen Ke, Hong Zhou, Gan Chen, Haibin Wang · 发表于：ACS Nano · 年份：2025 · DOI：10.1021/acsnano.4c14869 · 被引用次数：35 · 研究领域：Cardiac Fibrosis and Remodeling、Advanced Nanomaterials in Catalysis、Cardiac Ischemia and Reperfusion

Myocardial infarction (MI) poses a serious threat to human health. MI induces oxidative damage and inflammation, leading to myocardial death, scarring, and ventricular remodeling. Nanozymes have shown potential to alleviate reactive oxygen species (ROS)-induced damage and treat cardiovascular diseases. In this study, we developed an ultrasmall PtIr bimetallic nanozyme to treat MI. The PtIr nanozyme exhibited robust superoxide dismutase- and catalase-mimicking catalytic activities, modulating the conversion of excessive ROS into harmless products. Furthermore, PtIr nanozyme treatment reduced ROS levels and apoptosis in human cardiomyocyte AC16 cells under oxidative stress in vitro, while increasing the expression of cardiomyocyte-related functional genes, including cTnT, cTnI, Cx43, and ACTN2 . It also maintained the intracellular mitochondrial membrane potential, increased mitochondrial activity, and protected mitochondrial structure. In a rat MI model, the PtIr nanozyme attenuated neutrophil extracellular trap formation, apoptosis, and inflammation in the infarcted heart 1 week postadministration. Four weeks postadministration, the PtIr nanozyme significantly enhanced cardiomyocyte activity and functional connectivity, reduced infarct size and fibrosis levels, and increased microvascular density compared with phosphate-buffered saline or Ir nanozyme treatment. Proteomic analysis revealed that proteins associated with energy metabolism, mitochondrial function, and myocardial ...