Exosome-mediated targeted delivery of miR-210 for angiogenic therapy after cerebral ischemia in mice
Exosome-mediated targeted delivery of miR-210 for angiogenic therapy after cerebral ischemia in mice
复制标题
外泌体介导的 miR-210 靶向递送用于小鼠脑缺血后的血管生成治疗
DOI：
10.1186/s12951-019-0461-7
复制
发表时间：
2019-02-19
影响因子：
10.2
通讯作者：
Gao, Jun
中科院分区：
文献类型：
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作者：
Zhang, Huixin;Wu, Jin;Gao, Jun
研究背景越来越多的证据表明，microRNA-210（miR-210）在促进脑缺血后血管新生、促进脑组织修复方面具有重要的应用前景。然而，通过静脉内施用安全有效地递送miR-210仍然是一个挑战。在过去的十年中，外泌体已经成为一种新的内源性递送系统。在此，c（RGDyK）肽与外泌体结合，并负载胆固醇修饰的miR-210（RGD-exo：miR-210）。ResultsIn a transient middle cerebral artery occlusion（MCAO）mouse model，the RGD-exo：miR-210靶向于静脉给药后缺血脑的病变区域，导致该部位miR-210增加。此外，RGD-exo：miR-210隔日给药一次，持续14天，整合素β3、血管内皮生长因子（VEGF）和CD 34的表达显著上调。动物存活率也得到了提高。ConclusionsThese结果提示了一种将miR-210靶向递送至缺血性脑的策略，并为缺血性脑卒中的治疗提供了一种血管生成剂。
BackgroundAccumulating evidence shows that microRNA-210 (miR-210) holds great promise to improve angiogenesis for brain tissue repair after cerebral ischemia. However, safe and efficient delivery of miR-210 via intravenous administration is still a challenge. In the past decade, exosomes have emerged as a novel endogenous delivery system. Here, c(RGDyK) peptide is conjugated to exosomes, and they are loaded with cholesterol-modified miR-210 (RGD-exo:miR-210).ResultsIn a transient middle cerebral artery occlusion (MCAO) mouse model, the RGD-exo:miR-210 targets the lesion region of the ischemic brain after intravenous administration, resulting in an increase in miR-210 at the site. Furthermore, RGD-exo:miR-210 are administered once every other day for 14 days, and the expressions of integrin β3, vascular endothelial growth factor (VEGF) and CD34 are significantly upregulated. The animal survival rate is also enhanced.ConclusionsThese results suggest a strategy for the targeted delivery of miR-210 to ischemic brain and provide an angiogenic agent for the treatment of ischemic stroke.