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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Dendrimers / chemistry*
  • Genetic Therapy*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / genetics
  • Myocardial Infarction / genetics
  • Myocardial Infarction / pathology
  • Myocardial Infarction / therapy*
  • Myocardium / metabolism
  • Myocardium / pathology
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Receptor, Angiotensin, Type 1 / chemistry*
  • Receptor, Angiotensin, Type 1 / genetics

Substances

  • Dendrimers
  • MicroRNAs
  • Mirn1 microRNA, mouse
  • Receptor, Angiotensin, Type 1