单位：[1]Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, 99 Longcheng Street, Taiyuan 030032, China.[2]Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430030, China.华中科技大学同济医学院附属同济医院[3]Cardiology Department, First Hospital of Shanxi Medical University, 85 Jiefang South Road, Taiyuan 030032, China.[4]Department of Biochemistry and Molecular Biology, Shanxi Medical University, 56 Xinjian South Road, Taiyuan 030032, China.[5]The First Clinical Medical College, Shanxi Medical University, 85 Jiefang South Road, Taiyuan 030001, China.[6]The Radiology Department of Shanxi Provincial People's Hospital, The Fifth Hospital of Shanxi Medical University, Taiyuan 030001, China.
Myocardial infarction (MI) is the leading cause of death worldwide. The most effective way to treat myocardial infarction is to rescue ischemic cardiomyocytes. After an ischemic event, the overproduction of reactive oxygen species (ROS) is a key driver of myocardial injury. The produced ROS affects mitochondrial function and induces apoptosis in cardiomyocytes. This was accomplished by constructing platelet-membrane-encapsulated ROS-responsive drug-releasing nanoparticles (PMN@NIC-MalNPs) to deliver malonate and niclosamide (NIC). The results revealed that PMN@NIC-MalNPs degraded and released malonate and niclosamide in a high-level ROS microenvironment, effectively reducing the oxidative stress and apoptosis rate. By enhancing basal mitochondrial oxygen consumption rate (OCR), adenosine triphosphate (ATP) production, and spare respiratory capacity (SRC) in vitro, reduced the oxidative stress levels and restored mitochondrial function. In vivo studies revealed that the PMN@NIC-MalNPs improved cardiac dysfunction, inhibited succinate dehydrogenase (SDH) activity, increased ATP production, and reduced the myocardial infarct size in myocardial infarction model mice. Further, transcriptome analysis and Western blot revealed that PMN@NIC-MalNPs prevented apoptosis by activating the expressions of the signal transducer and activator of transcription 3 (STAT3) and Bcl-2, and inhibiting the expression of Bax. Thus, this study provides a novel therapeutic solution for treating myocardial infarction and predicting the viability of an antioxidant and antiapoptotic therapeutic solution in the treatment of myocardial injury.
基金：
This work has been financially supported by the National Key
R&D Program of China (No:2023YFC3402800); National
Natural Science Foundation of China (No: 82120108016,
82071987, 32201165); China Postdoctoral Science Foundation (No: 2023M742178); Key Laboratory of Nanoimaging
and Drug-loaded Preparation of Shanxi Province (NO:
202104010910010); Fundamental Research Program of Shanxi
Province (NO: 20210302124401, 20210302123413); Scientific
Research Foundation of Shanxi Bethune Hospital (NO:
2021RC012, 2021RC040).
第一作者单位：[1]Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, 99 Longcheng Street, Taiyuan 030032, China.[2]Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430030, China.
共同第一作者：
通讯作者：
通讯机构：[1]Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, 99 Longcheng Street, Taiyuan 030032, China.[2]Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430030, China.
推荐引用方式(GB/T 7714)：
Hu Nan,Sun Meng,Lv Nan,et al.ROS-Suppression Nanoplatform Combined Activation of STAT3/Bcl-2 Pathway for Preventing Myocardial Infarction in Mice[J].ACS APPLIED MATERIALS & INTERFACES.2024,16(10):12188-12201.doi:10.1021/acsami.3c16735.
APA：
Hu Nan,Sun Meng,Lv Nan,Gao Yangyang,Fu Xiaohong...&Zhang Ruiping.(2024).ROS-Suppression Nanoplatform Combined Activation of STAT3/Bcl-2 Pathway for Preventing Myocardial Infarction in Mice.ACS APPLIED MATERIALS & INTERFACES,16,(10)
MLA：
Hu Nan,et al."ROS-Suppression Nanoplatform Combined Activation of STAT3/Bcl-2 Pathway for Preventing Myocardial Infarction in Mice".ACS APPLIED MATERIALS & INTERFACES 16..10(2024):12188-12201
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