Enhanced Local Delivery of microRNA-145a-5P into Mouse Aorta via Ultrasound-Targeted Microbubble Destruction Inhibits Atherosclerotic Plaque Formation.
Enhanced Local Delivery of microRNA-145a-5P into Mouse Aorta via Ultrasound-Targeted Microbubble Destruction Inhibits Atherosclerotic Plaque Formation.
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DOI：
10.1021/acs.molpharmaceut.2c00799
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发表时间：
2023-01
影响因子：
4.9
通讯作者：
Yu Wu;Cheng Deng;Jia Xu;Wei Wang;Yihan Chen;Xiaojuan Qin;Q. Lv;M. Xie
中科院分区：
文献类型：
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作者：
Yu Wu;Cheng Deng;Jia Xu;Wei Wang;Yihan Chen;Xiaojuan Qin;Q. Lv;M. Xie
血管平滑肌细胞（VSMCs）的异常增殖和迁移在动脉粥样硬化斑块的形成和破裂中起关键作用。已有研究证实microRNA-145（miR-145）参与了VSMCs的表型调控和动脉粥样硬化的减轻。目前，寻求安全、有效的基因递送仍然是制约基因治疗发展的关键问题。近年来，超声靶向微泡破坏（Ultrasound-targeted microbubble destruction，UTMD）已成为一种安全有效的转染方法，广泛应用于心脏和肿瘤疾病基因治疗的基础研究。在这里，我们合成了阳离子微泡来封装miR-145，并使用超声在体外和体内将其靶向释放到VSMC中。该基因治疗的可行性通过荧光显微镜和体内成像系统进行了验证。结果表明，UTMD介导的miR-145处理显著提高了VSMCs的基因转染效率，并促进了VSMCs的收缩表型。在体内，与游离miR-145治疗相比，该治疗使动脉粥样硬化斑块面积减少了48.04%。因此，UTMD介导的miRNA治疗可能为动脉粥样硬化斑块提供一种新的靶向治疗方法。
Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) play a key role in the formation and rupture of atherosclerotic plaques. Previous studies have confirmed that microRNA-145 (miR-145) is involved in the phenotypic regulation of VSMCs and reduction of atherosclerosis. At present, seeking safe and effective gene delivery remains a key problem restricting the development of gene therapy. In recent years, ultrasound-targeted microbubble destruction (UTMD) has become a safe and effective transfection method that is widely used in the basic research of gene therapy for heart and tumor diseases. Here, we synthesized cationic microbubbles to encapsulate miR-145 and targeted their release into VSMCs in vitro and in vivo using ultrasound. The feasibility of this gene therapy was verified by fluorescence microscopy and an in vivo imaging system. The results showed that treatment with miR-145 delivered via UTMD considerably improved the gene transfection efficiency and promoted the contraction phenotype of VSMCs in vitro. In vivo, this treatment reduced the atherosclerotic plaque area by 48.04% compared with treatment with free miR-145. Therefore, UTMD-mediated miRNA therapy may provide a new targeted therapeutic approach for atherosclerotic plaques.