Treating myocardial infarction via a nano-ultrasonic contrast agent-mediated high-efficiency drug delivery system targeting macrophages
Zhen Ma, Ming Li, Rui Guo, Yu Tian, Yongbin Zheng, Bingxin Huang, Yi You, Qing Xu, Ming Cui, Li Shen, Lan Feng, Hang Yang, Rucong Liu, Tao Yang, Feng Wan, Qihua He, Xiao Huo, Youkun Bi, Yingying Zhang, Yunpeng Ling
Abstract
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-NO 2 ) into CD86-positive macrophages. Upon irradiation with low-intensity focused ultrasound, FA-PNBs release siSTAT1 and OA-NO 2 at the ischemic injury zone. The results demonstrated the system’s precise targeting and efficient delivery capabilities. The combined modulation of OA-NO 2 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.