Targeted gene delivery to ischemic myocardium by homing peptide-guided polymeric carrier

Young Wook Won, Arlo N. McGinn, Minhyung Lee, David A. Bull, Sung Wan Kim

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Myocardial ischemia needs an alternative treatment such as gene therapy for the direct protection of cardiomyocytes against necrosis or apoptosis and to prevent the development of myocardial fibrosis and cardiac dysfunction. Despite the utility of gene therapy, its therapeutic use is limited due to inadequate transfection in cardiomyocytes and difficulty in directing to ischemic myocardium. Here, we present a polymeric gene carrier that is capable of targeting ischemic myocardium, resulting in high localization within the ischemic zone of the left ventricle (LV) of an ischemia/reperfusion (I/R) rat model upon systemic administration. Cystamine bisacrylamide-diamino hexane (CD) polymer was modified with the ischemic myocardium-targeted peptide (IMTP) and d-9-arginine (9R) for dual effects of the homing to ischemic myocardium and enhanced transfection efficiency with minimized polymer use. Conjugation of IMTP and 9R to CD led to an increase in transfection under hypoxia and significantly reduced the amount of polymer required for high transfection. Finally, we confirmed targeting of IMTP-CD-9R/DNA polyplex to ischemic myocardium and enhanced gene expression in LV of the I/R rat after tail vein injection. This study provides a clue that gene therapy for the treatment of myocardial ischemia can be achieved by using homing peptide-guided gene delivery systems.

Original languageEnglish (US)
Pages (from-to)378-385
Number of pages8
JournalMolecular Pharmaceutics
Volume10
Issue number1
DOIs
StatePublished - Jan 7 2013
Externally publishedYes

Keywords

  • gene therapy
  • homing peptide
  • ischemic myocardium targeting
  • myocardial ischemia
  • targeted gene delivery

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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