Cardiac RNAi therapy using RAGE siRNA/deoxycholic acid-modified polyethylenimine complexes for myocardial infarction

Jueun Hong, Sook Hee Ku, Min Sang Lee, Ji Hoon Jeong, Hyejung Mok, Donghoon Choi, Sun Hwa Kim

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Inflammatory response in myocardial ischemia-reperfusion injury plays a critical role in ventricular remodeling. To avoid deleterious effects of overwhelming inflammation, we blocked the expression of receptor for advanced glycation end-products (RAGE), a key mediator of the local and systemic inflammatory responses, via RNAi mechanism. Herein, a facial amphipathic deoxycholic acid-modified low molecular weight polyethylenimine (DA-PEI) was used as a siRNA delivery carrier to myocardium. The DA-PEI conjugate formed a stable complex with siRNA via electrostatic and hydrophobic interactions. The siRAGE/DA-PEI formulation having negligible toxicity could enhance intracellular delivery efficiency and successfully suppress RAGE expression both invitro and invivo. Furthermore, the cardiac administration of siRAGE/DA-PEI reduced apoptosis and inflammatory cytokine release, subsequently led to attenuation of left ventricular remodeling in rat myocardial infarction model. The potential therapeutic effects of RAGE gene silencing on myocardial ischemia-reperfusion injury may suggest that the siRAGE/DA-PEI delivery system can be considered as a promising strategy for treating myocardial infarction.

Original languageEnglish (US)
Pages (from-to)7562-7573
Number of pages12
JournalBiomaterials
Volume35
Issue number26
DOIs
StatePublished - Aug 2014

Keywords

  • Deoxycholic acid-modified polyethylenimine
  • Myocardial ischemia-reperfusion injury
  • RAGE siRNA
  • SiRNA delivery

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