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 journalArticle

22 Citations (Scopus)

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
Pages (from-to)7562-7573
Number of pages12
JournalBiomaterials
Volume35
Issue number26
DOIs
Publication statusPublished - 2014 Jan 1

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Polyethyleneimine
Polyetherimides
Deoxycholic Acid
Small Interfering RNA
Myocardial Reperfusion Injury
Ventricular Remodeling
Myocardial Infarction
Reperfusion Injury
Myocardial Ischemia
Acids
Gene Silencing
Therapeutic Uses
RNA Interference
Static Electricity
Hydrophobic and Hydrophilic Interactions
Myocardium
Molecular Weight
Cytokines
Inflammation
Cell death

All Science Journal Classification (ASJC) codes

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

Cite this

Hong, Jueun ; Ku, Sook Hee ; Lee, Min Sang ; Jeong, Ji Hoon ; Mok, Hyejung ; Choi, Donghoon ; Kim, Sun Hwa. / Cardiac RNAi therapy using RAGE siRNA/deoxycholic acid-modified polyethylenimine complexes for myocardial infarction. In: Biomaterials. 2014 ; Vol. 35, No. 26. pp. 7562-7573.
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Cardiac RNAi therapy using RAGE siRNA/deoxycholic acid-modified polyethylenimine complexes for myocardial infarction. / Hong, Jueun; Ku, Sook Hee; Lee, Min Sang; Jeong, Ji Hoon; Mok, Hyejung; Choi, Donghoon; Kim, Sun Hwa.

In: Biomaterials, Vol. 35, No. 26, 01.01.2014, p. 7562-7573.

Research output: Contribution to journalArticle

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