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Nanomedicine. 2018 Feb;14(2):619-631. doi: 10.1016/j.nano.2017.12.004. Epub 2017 Dec 18.

Delivery of microRNA-1 inhibitor by dendrimer-based nanovector: An early targeting therapy for myocardial infarction in mice.

Author information

1
Department of Anesthesiology and SICU, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
2
Institute for Biomedical Engineering &Nano Science, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
3
The Materials Science & Engineering Program, Department of Mechanical & Materials Engineering, College of Engineering & Applied Science, University of Cincinnati, Cincinnati, OH, USA.
4
Department of Anesthesiology and SICU, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: hebin@xinhuamed.com.cn.
5
Institute for Biomedical Engineering &Nano Science, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: yongyong_li@tongji.edu.cn.

Abstract

Myocardial infarction (MI), known to be rapidly progressed and fatal, necessitates a timely and effective intervention particularly within golden 24 h. The crux is to develop a therapeutic agent that can early target the infarct site with integrated therapeutic capacity. Finding the AT1 receptor being most over-expressed at 24 h after MI, we developed a nanovector (AT1-PEG-DGL) anchored with AT1 targeting peptide, and simultaneously armed it with specific microRNA-1 inhibitor (AMO-1) to attenuate cardiomyocyte apoptosis. In vivo imaging after IV administration demonstrated that AT1-PEG-DGL quickly accumulated in the MI heart during the desired early period, significantly outperforming the control group without AT1 targeting. Most importantly, a pronounced in-vivo anti-apoptosis effect was observed upon a single IV injection. Apoptotic cell death in the infarct border zone was significantly decreased and the myocardial infarct size was reduced by 64.1% as compared with that in MI control group, promising for early MI treatment.

KEYWORDS:

Dendrigraft poly-(L)-lysine; Early targeting therapy; Myocardial infarction; Nanovector; miRNA-1

PMID:
29269324
DOI:
10.1016/j.nano.2017.12.004
[Indexed for MEDLINE]

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