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

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 β 3 , 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. Electronic supplementary material The online version of this article (10.1186/s12951-019-0461-7) contains supplementary material, which is available to authorized users.

Human iPS Cells Derived Skeletal Muscle Progenitor Cells Promote Myoangiogenesis and Restore Dystrophin in Duchenne Muscular Dystrophic Mice

“…Activation of miR-17-92 cluster promoted angiogenesis via PTEN signaling pathway, however, EC miR-17-92 cluster knockout impaired angiogenesis (36). miR-181a and miR-210 are also reported to promote angiogenesis (37)(38)(39)(40). Thus it is very likely that Givi-MPC interacted with resident EC to initiate myogenesis and angiogenesis in Mdx/SCID mice after CTX injury.…”

Lab-On-A-Chip for the Development of Pro-/Anti-Angiogenic Nanomedicines to Treat Brain Diseases

“…More importantly, they can be specifically functionalized to target particular pathways and sites on the BMECs. They are designed to have greater BBB permeability [2,6,9,11,17,19], stability [5,9], half-life [11,18,82,83] and shelf-life [5], high-site specific targeting [10,14,84], and a controlled load-release of drugs [18,19,21,84,85].…”

“…The exosomes are nothing but naturally occurring liposomes, also made of phospholipids, a sub-group of extracellular vesicles, with a size range from 50 nm to 120 nm. They are highly biocompatible and readily internalized by brain cells [17]. Nano-scaffolds made from cationic polysaccharides/polymers (10-1000 nm) have been used to adsorb the drug and facilitate its transport across the BBB by masking the drug's steric effect [20,21].…”

“…The brain stroke, which is caused by the constriction of brain blood vessels or hemorrhage requires immediate treatment as the therapeutic window is only 3-4.5 h. Restoring blood circulation and controlling vascular degeneration through angiogenesis are the major strategies for the above conditions. Various pro-angiogenic materials have been reported, some of which already are available as NMs such as Simvastatin [11], VEGF [18,87], nitric oxide (NO) donors [21], ZL006 [10], Cyclosporine A (CsA) [12], and microRNAs [14,17] (see Table 1).…”

“…Recently, NMs have been investigated for their efficacy in treating brain angiogenesis conditions. These have included nano-capsules, such as solid lipid nanoparticles (SLNs) [4][5][6][7][8], liposomes [9][10][11][12][13][14][15][16], exosomes [17], and others [18], as well as nano-scaffolds made of chitosan [19], polymers [20,21], inorganic nanoparticles (NPs) [22][23][24], etc. (see Table 1).…”