miRNA transfection via poly(amidoamine)-based delivery vector prevents hypoxia/reperfusion-induced cardiomyocyte apoptosis

Nanomedicine (Lond). 2020 Jan;15(2):163-181. doi: 10.2217/nnm-2019-0363. Epub 2019 Dec 4.

Abstract

Aim: Myocardial infarction is a tissue injury that leads to apoptosis of cardiomyocytes. This can be prevented by using miRNAs, but its delivery to cardiomyocytes is a major hurdle. We aimed to deliver miRNAs using poly(amidoamine)-histidine (PAMAM-His) nanocarriers to prevent apoptosis. Materials & methods: The PAMAM-His nanoparticles were synthesized and assessed for their transfection efficiency of miRNAs to prevent apoptosis in hypoxia/reperfusion-induced H9c2 as well as primary cultured cardiomyocytes. Results & conclusion: miRNAs-nanoparticle complexes exerted a significant antiapoptotic effect on the H9c2 and primary rat ventricular cardiomyocytes. Enhanced expression of antiapoptotic genes and decreased expression of proapoptotic genes were observed. PAMAM-His nanoparticles effectively delivered miRNAs to the cardiomyocytes and prevented the hypoxia/reperfusion-induced apoptosis critical in myocardial infarctions.

Keywords: PAMAM dendrimers; RNA interference; cardiomyocytes; hypoxia/reperfusion injury; miRNA; myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Gene Transfer Techniques*
  • Genetic Vectors / chemistry
  • Genetic Vectors / pharmacology
  • Histidine / chemistry
  • Histidine / pharmacology
  • Humans
  • MicroRNAs / pharmacology*
  • Myocardial Infarction / genetics
  • Myocardial Infarction / pathology
  • Myocardial Infarction / therapy*
  • Myocardial Reperfusion Injury / genetics
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / therapy*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Nanoparticles / chemistry
  • Polyamines / chemistry
  • Polyamines / pharmacology
  • Rats
  • Signal Transduction / drug effects
  • Transfection

Substances

  • MicroRNAs
  • Poly(amidoamine)
  • Polyamines
  • Histidine