Following myocardial infarction (MI), the accumulation of CD86-positive macrophages in the ischemic injury zone leads to secondary myocardial damage. Precise pharmacological intervention targeting this process remains challenging. This study engineered a nanotherapeutic delivery system with CD86-positive macrophage-specific targeting and ultrasound-responsive release capabilities. A folic acid (FA)-modified ultrasound-responsive gene/drug delivery system, assembled from DOTAP, DSPE-PEG2000-FA, cholesterol, and perfluorohexane (PFH)-termed FA-PNBs-was developed to codeliver small interfering RNA of STAT1 (siSTAT1) and the small-molecule nitro-oleic acid (OA-NO2) into CD86-positive macrophages. Upon irradiation with low-intensity focused ultrasound, FA-PNBs release siSTAT1 and OA-NO2 at the ischemic injury zone. The results demonstrated the system's precise targeting and efficient delivery capabilities. The combined modulation of OA-NO2 and siSTAT1 optimizes the immune microenvironment in the infarcted region, alleviates ventricular remodeling, preserves cardiac function, and holds promise for clinical intervention strategies after MI.
基金：
National Natural Science Foundation of China [82202791, 82172538]; Michigan Medicine- PKUHSC Joint Institute for Translational and Clinical Research [BMU2022JI006]
第一作者机构：[1]Peking Univ Third Hosp, Dept Cardiac Surg, Beijing 100191, Peoples R China[2]Joint Int Res Ctr Translat & Clin Res, Beijing 100142, Peoples R China[3]Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing Key Lab Mol Pharmaceut & Drug Delivery Sys, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China[4]Peking Univ, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Peking Univ Third Hosp, Dept Cardiac Surg, Beijing 100191, Peoples R China[2]Joint Int Res Ctr Translat & Clin Res, Beijing 100142, Peoples R China[3]Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing Key Lab Mol Pharmaceut & Drug Delivery Sys, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China[4]Peking Univ, Sch Pharmaceut Sci, Beijing 100191, Peoples R China[15]Xuzhou Med Univ, Sch Med Imaging, Xuzhou 221006, Peoples R China
推荐引用方式(GB/T 7714)：
Ma Zhen,Li Ming,Guo Rui,et al.Treating myocardial infarction via a nano-ultrasonic contrast agent-mediated high-efficiency drug delivery system targeting macrophages[J].SCIENCE ADVANCES.2025,11(1):doi:10.1126/sciadv.adp7126.
APA：
Ma, Zhen,Li, Ming,Guo, Rui,Tian, Yu,Zheng, Yongbin...&Ling, Yunpeng.(2025).Treating myocardial infarction via a nano-ultrasonic contrast agent-mediated high-efficiency drug delivery system targeting macrophages.SCIENCE ADVANCES,11,(1)
MLA：
Ma, Zhen,et al."Treating myocardial infarction via a nano-ultrasonic contrast agent-mediated high-efficiency drug delivery system targeting macrophages".SCIENCE ADVANCES 11..1(2025)
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