Exosome-mediated targeted delivery of miR-210 for angiogenic therapy after cerebral ischemia in mice

Huixin Zhang†,
Jin Wu†,
Jiahuan Wu,
Qi Fan,
Jingchao Zhou,
Junwen Wu,
Sichen Liu,
Jie Zang,
Jinhai Ye,
Ming XiaoEmail author,
Tian TianEmail author and
Jun GaoEmail author View ORCID ID profile

†Contributed equally

Journal of Nanobiotechnology201917:29

https://doi.org/10.1186/s12951-019-0461-7

Received: 23 October 2018
Accepted: 23 January 2019
Published: 19 February 2019

Abstract

Background

Accumulating 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).

Results

In 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.

Conclusions

These 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.