一氧化氮
线粒体通透性转换孔
活性氧
药理学
纳米笼
细胞凋亡
体内
一氧化氮合酶
再灌注损伤
缺血
化学
医学
程序性细胞死亡
生物化学
生物
内科学
生物技术
催化作用
作者
Zekun Wang,Nana Yang,Ya‐Jun Hou,Yuqing Li,Chenyang Yin,Endong Yang,Huanhuan Cao,Gaofei Hu,Jing Xue,Jialei Yang,Ziyu Liao,Weiyun Wang,Dongdong Sun,Cundong Fan,Lemin Zheng
标识
DOI:10.1002/advs.202302123
摘要
Cardiovascular disease is the leading cause of death worldwide. Reperfusion therapy is vital to patient survival after a heart attack but can cause myocardial ischemia/reperfusion injury (MI/RI). Nitric oxide (NO) can ameliorate MI/RI and is a key molecule for drug development. However, reactive oxygen species (ROS) can easily oxidize NO to peroxynitrite, which causes secondary cardiomyocyte damage. Herein, L-arginine-loaded selenium-coated gold nanocages (AAS) are designed, synthesized, and modified with PCM (WLSEAGPVVTVRALRGTGSW) to obtain AASP, which targets cardiomyocytes, exhibits increased cellular uptake, and improves photoacoustic imaging in vitro and in vivo. AASP significantly inhibits oxygen glucose deprivation/reoxygenation (OGD/R)-induced H9C2 cell cytotoxicity and apoptosis. Mechanistic investigation revealed that AASP improves mitochondrial membrane potential (MMP), restores ATP synthase activity, blocks ROS generation, and prevents NO oxidation, and NO blocks ROS release by regulating the closing of the mitochondrial permeability transition pore (mPTP). AASP administration in vivo improves myocardial function, inhibits myocardial apoptosis and fibrosis, and ultimately attenuates MI/RI in rats by maintaining mitochondrial function and regulating NO signaling. AASP shows good safety and biocompatibility in vivo. This findings confirm the rational design of AASP, which can provide effective treatment for MI/RI.
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