Facial amphipathic deoxycholic acid-modified polyethyleneimine for efficient MMP-2 siRNA delivery in vascular smooth muscle cells

Dongkyu Kim, Dokyoung Lee, Yeon Lim Jang, Su Young Chae, Donghoon Choi, Ji Hoon Jeong, Sun Hwa Kim

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38 Citations (Scopus)


Clinical applications of RNA interference-based therapeutics such as small interfering RNAs (siRNAs) have been limited mainly due to low intracellular delivery efficiency in vitro and in vivo. In this study, facially amphipathic deoxycholic acid (DA)-modified polyethyleneimine (PEI 1.8) (DA-PEI 1.8) was synthesized and used as a potent carrier system for siRNA targeted against matrix metalloproteinase-2 (MMP-2) to inhibit the migration of vascular smooth muscle cells (SMCs), which is the major pathomechanism in the development of atherosclerosis and restenosis after arterial injury. A representative facial amphipathic bile acid DA having a high membrane permeability was conjugated to the terminal amine groups of the low molecular weight PEI 1.8 via amide bonds. The DA-PEI 1.8 conjugates formed self-assembled nanoparticles with siRNA molecules in an aqueous phase and the DA-PEI 1.8/siRNA polyplexes became stabilized and condensed as particle incubation time increased from 0 to 4 h. Both cellular internalization and target gene silencing were enhanced as the DA-PEI 1.8/siRNA polyplexes stabilized. When vascular SMCs were transfected with MMP-2 siRNA, the DA-PEI 1.8/siRNA polyplex formulation led to a significant decrease in MMP-2 gene expression, resulting in the suppression of cell migration. These results suggest that the DA-PEI 1.8/MMP-2 siRNA delivery system may be useful in anti-restenotic treatment for various vasculoproliferative disorders such as atherosclerosis, in-stent restenosis, and vein graft failure.

Original languageEnglish
Pages (from-to)14-23
Number of pages10
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Issue number1
Publication statusPublished - 2012 May

Bibliographical note

Funding Information:
Grants from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A085136 and A110879) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0022471) supported this work.

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Pharmaceutical Science


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