Self-assembly of stem cell membrane-camouflaged nanocomplex for microRNA-mediated repair of myocardial infarction injury
Self-assembly of stem cell membrane-camouflaged nanocomplex for microRNA-mediated repair of myocardial infarction injury
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干细胞膜伪装纳米复合物自组装用于microRNA介导的心肌梗死损伤修复
DOI：
10.1016/j.biomaterials.2020.120256
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发表时间：
2020
期刊：
影响因子：
14
通讯作者：
Dayong Yang
中科院分区：
文献类型：
--
作者：
Chi Yao;Weijian Wu;Han Tang;Xuemei Jia;Jianpu Tang;Xinhua Ruan;Feng Li;David Tai Leong;Dan Luo;Dayong Yang
间充质干细胞来源的外泌体在心肌梗死（MI）治疗中显示出良好的疗效。使用外泌体的主要障碍仍然是由于细胞培养的低产量以及复杂的纯化过程。在这里，我们报道了干细胞膜伪装的模仿外泌体的纳米复合物的自组装，该复合物概括了外泌体的功能，实现了有效的microRNA （miRNA）递送和miRNA介导的心肌修复。该纳米复合物是通过间充质干细胞膜在负载miRNA的介孔二氧化硅纳米颗粒表面的自组装而构建的，具有较高的miRNA负载能力，并保护miRNA在体液中不被降解。纳米复合物可以逃避免疫系统的清除，并靶向缺血性损伤的心肌细胞。miRNA被触发释放并与靶mRNA结合，抑制凋亡相关蛋白的翻译，从而促进心肌细胞的增殖。在心肌梗死小鼠模型中，外泌体模拟纳米复合物的使用有效地保护了存活心肌并增强了心功能。
Mesenchymal stem cells-derived exosomes have shown promising therapeutic effect on myocardial infarction (MI). The major hurdles remain for the use of exosomes primarily due to the low yields from cell cultures coupled with complicated purification processes. Herein we report the self-assembly of stem cell membrane-camouflaged exosome-mimicking nanocomplex that recapitulates exosome functions, achieving efficient microRNA (miRNA) delivery and miRNA-mediated myocardial repair. The nanocomplex is constructed via the self-assembly of mesenchymal stem cell membrane on miRNA loaded mesoporous silica nanoparticle surface, which enables high miRNA loading capacity and protects miRNA from degradation in body fluid. The nanocomplex can escape the clearance of immunologic system, and target to ischemic injured cardiomyocytes. miRNA is triggered to release and binds to target mRNA, which inhibits the translation of apoptosis-related proteins, and consequently promotes the proliferation of cardiomyocytes. In the MI mouse model, the administration of exosome-mimicking nanocomplex effectively leads to preservation of viable myocardium and augmentation of cardiac functions.