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 h...

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Main Authors: Huixin Zhang, Jin Wu, Jiahuan Wu, Qi Fan, Jingchao Zhou, Junwen Wu, Sichen Liu, Jie Zang, Jinhai Ye, Ming Xiao, Tian Tian, Jun Gao
Format: Article
Language:English
Published: BMC 2019-02-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12951-019-0461-7
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author Huixin Zhang
Jin Wu
Jiahuan Wu
Qi Fan
Jingchao Zhou
Junwen Wu
Sichen Liu
Jie Zang
Jinhai Ye
Ming Xiao
Tian Tian
Jun Gao
author_facet Huixin Zhang
Jin Wu
Jiahuan Wu
Qi Fan
Jingchao Zhou
Junwen Wu
Sichen Liu
Jie Zang
Jinhai Ye
Ming Xiao
Tian Tian
Jun Gao
author_sort Huixin Zhang
collection DOAJ
description 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.
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spelling doaj.art-a52e965a50fd4eb3854314159eba70882022-12-22T03:59:25ZengBMCJournal of Nanobiotechnology1477-31552019-02-0117111310.1186/s12951-019-0461-7Exosome-mediated targeted delivery of miR-210 for angiogenic therapy after cerebral ischemia in miceHuixin Zhang0Jin Wu1Jiahuan Wu2Qi Fan3Jingchao Zhou4Junwen Wu5Sichen Liu6Jie Zang7Jinhai Ye8Ming Xiao9Tian Tian10Jun Gao11The Department of Neurobiology, Key Laboratory of Human Functional Genomics of Jiangsu, Nanjing Medical UniversityThe Department of Neurology, The Second Affiliated Hospital of Nanjing Medical UniversityThe Department of Neurobiology, Key Laboratory of Human Functional Genomics of Jiangsu, Nanjing Medical UniversityThe School of Basic Medical Science, Nanjing Medical UniversityThe School of Basic Medical Science, Nanjing Medical UniversityThe School of Basic Medical Science, Nanjing Medical UniversityThe School of Basic Medical Science, Nanjing Medical UniversityThe School of Basic Medical Science, Nanjing Medical UniversityThe Department of Oral and Maxillofacial Surgery, The Affiliated Stomatology Hospital of Nanjing Medical University, Nanjing Medical UniversityJiangsu Key Laboratory of Neurodegeneration, Nanjing Medical UniversityThe Department of Neurobiology, Key Laboratory of Human Functional Genomics of Jiangsu, Nanjing Medical UniversityThe Department of Neurobiology, Key Laboratory of Human Functional Genomics of Jiangsu, Nanjing Medical UniversityAbstract 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.http://link.springer.com/article/10.1186/s12951-019-0461-7IschemiamiR-210ExosomesAngiogenesis
spellingShingle Huixin Zhang
Jin Wu
Jiahuan Wu
Qi Fan
Jingchao Zhou
Junwen Wu
Sichen Liu
Jie Zang
Jinhai Ye
Ming Xiao
Tian Tian
Jun Gao
Exosome-mediated targeted delivery of miR-210 for angiogenic therapy after cerebral ischemia in mice
Journal of Nanobiotechnology
Ischemia
miR-210
Exosomes
Angiogenesis
title Exosome-mediated targeted delivery of miR-210 for angiogenic therapy after cerebral ischemia in mice
title_full Exosome-mediated targeted delivery of miR-210 for angiogenic therapy after cerebral ischemia in mice
title_fullStr Exosome-mediated targeted delivery of miR-210 for angiogenic therapy after cerebral ischemia in mice
title_full_unstemmed Exosome-mediated targeted delivery of miR-210 for angiogenic therapy after cerebral ischemia in mice
title_short Exosome-mediated targeted delivery of miR-210 for angiogenic therapy after cerebral ischemia in mice
title_sort exosome mediated targeted delivery of mir 210 for angiogenic therapy after cerebral ischemia in mice
topic Ischemia
miR-210
Exosomes
Angiogenesis
url http://link.springer.com/article/10.1186/s12951-019-0461-7
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