Enhanced Cytoplasmic Delivery of RAGE siRNA Using Bioreducible Polyethylenimine-based Nanocarriers for Myocardial Gene Therapy

Min Jung Yang, Sook Hee Ku, Dongkyu Kim, Won Jong Kim, Hyejung Mok, Sun Hwa Kim, Ick Chan Kwon

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

This study aims to develop bioreducible polyethylenimine (rPEI)/siRNA polyplexes with high stability, high transfection efficiency, and low cytotoxicity for efficient cytoplasmic siRNA delivery. rPEI successfully incorporated siRNA into stable and compact nanocomplexes, and the disulfide linkages in rPEI/siRNA were cleaved under reductive environments, resulting in efficient intracellular translocation and siRNA release. In this study, receptor for advanced glycation end-products (RAGE) was selected as a therapeutic target gene because it is associated with inflammatory responses in ischemia/reperfusion injury. rPEI/siRAGE exhibited high target gene silencing and low cytotoxicity in cardiomyocytes, and the treatment of rPEI/siRAGE reduced the myocardial infarction size. Bioreducible polyethylenimine (rPEI) is synthesized from low molecular weight PEI via cleavable disulfide linkages to achieve high stability, high transfection efficiency, high cytoplasmic siRNA release, and low cytotoxicity. rPEI/siRAGE polyplex can reduce RAGE expression in ischemic/reperfused myocardium, thereby leading to attenuation of myocardial infarction.

Original languageEnglish
Pages (from-to)1755-1763
Number of pages9
JournalMacromolecular Bioscience
Volume15
Issue number12
DOIs
Publication statusPublished - 2015 Dec 1
Externally publishedYes

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Keywords

  • bioreducible polyethylenimine
  • cytoplasmic delivery
  • myocardial infarction
  • RAGE
  • siRNA

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

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