Yao Chi, Wu Weijian, Tang Han, Jia Xuemei, Tang Jianpu, Ruan Xinhua, Li Feng, Leong David Tai, Luo Dan, Yang Dayong
Frontier Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, PR China.
Department of Cardiac Surgery, Tianjin Union Medical Centre, Tianjin, 300121, PR China.
Biomaterials. 2020 Oct;257:120256. doi: 10.1016/j.biomaterials.2020.120256. Epub 2020 Jul 25.
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.
间充质干细胞衍生的外泌体已显示出对心肌梗死（MI）有良好的治疗效果。外泌体使用的主要障碍仍然存在，主要是因为细胞培养产量低以及纯化过程复杂。在此，我们报告了干细胞膜伪装的外泌体模拟纳米复合物的自组装，其概括了外泌体的功能，实现了有效的微小RNA（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自组装构建而成，这使得miRNA具有高负载能力，并保护miRNA在体液中不被降解。该纳米复合物可以逃避免疫系统的清除，并靶向缺血损伤的心肌细胞。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MI小鼠模型中，给予外泌体模拟纳米复合物有效地导致存活心肌的保留和心脏功能的增强。
