Primary cardiomyocyte-targeted bioreducible polymer for efficient gene delivery to the myocardium

Hye Y. Nam, Arlo McGinn, Pyung Hwan Kim, Sung W. Kim, David A. Bull

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

A cardiomyocyte-targeted Fas siRNA delivery system was developed using primary cardiomyocyte (PCM) specific peptide-modified polymers with high transfection efficiency and low cytotoxicity. Primary cardiomyocyte (PCM) specific peptide, selected by phage display, was conjugated to bioreducible poly(cystamine bisacrylamide-diaminohexane, CBA-DAH) (PCD). The specificity of the PCM-modified polymer to cardiomyocytes was confirmed by competition study with free PCM ligand and by delivery to non-cardiomyocyte NIH 3T3 fibroblasts. The cellular binding and uptake of the PCM-polymer/pDNA polyplex was inhibited by addition of free PCM peptide. The impact of PCM conjugation on cellular uptake and transfection efficiency was greater in H9C2 rat cardiomyocytes than in NIH 3T3 cells. Fas siRNA/PCM-polymer polyplexes exhibited significant Fas gene silencing in rat cardiomyocytes under hypoxic conditions, leading to inhibition of cardiomyocyte apoptosis. These findings demonstrate the utility of the addition of a primary cardiomyocyte (PCM) specific peptide modification to a bioreducible polymer for targeted delivery of Fas siRNA to inhibit cardiomyocyte apoptosis.

Original languageEnglish (US)
Pages (from-to)8081-8087
Number of pages7
JournalBiomaterials
Volume31
Issue number31
DOIs
StatePublished - Nov 2010
Externally publishedYes

Keywords

  • Bioreducible polymer
  • Cardiomyocyte
  • Fas
  • PCM
  • SiRNA

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Fingerprint

Dive into the research topics of 'Primary cardiomyocyte-targeted bioreducible polymer for efficient gene delivery to the myocardium'. Together they form a unique fingerprint.

Cite this