Bioreducible crosslinked polyelectrolyte complexes for MMP-2 siRNA delivery into human vascular smooth muscle cells

Dokyoung Lee, Dongkyu Kim, Hyejung Mok, Ji Hoon Jeong, Donghoon Choi, Sun Hwa Kim

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19 Citations (Scopus)


Purpose Bioreducible crosslinked polyplexes were prepared via disulfide bond formation after siRNA condensation with polyethylenimine-modified by deoxycholic acid (PEI-DA) to stabilize polyplex structure in an extracellular environment and to promote transfection efficiency in human smooth muscle cells (hSMCs). Methods The PEI-DA/siRNA polyplexes were further modified by crosslinking the primary amines of PEI with thiol-cleavable crosslinkers. The effect of disulfide crosslinked PEI-DA/siRNA (Cr PEIDA/ siRNA) polyplexes on target gene silencing was investigated by transfecting hSMCs with matrix metalloproteinase-2 (MMP-2) siRNA under serum conditions. The MMP-2 levels in the conditioned medium were examined using gelatin zymography. Results The Cr PEI-DA/siRNA polyplexes showed increased stability against heparin exchange reactions,while their disulfide linkages were successfully cleaved under reducing conditions. The polyplex crosslinking reaction led to a slight decrease inMMP-2 gene silencing activity in hSMCs due to the insufficient redox potential. However, the gene silencing efficiency of the Cr PEI-DA/siRNA polypexes was gradually improved in response to increasing intracellular reduction potential. The increased serum stability of the Cr PEI-DA/siRNA polyplexes resulted in significant enhancement of the intracellular delivery efficiency especially under serum conditions. Conclusion The Cr PEI-DA/siRNA polyplex formulation may be a promising siRNA delivery system for the treatment of incurable genetic disorders.

Original languageEnglish
Pages (from-to)2213-2224
Number of pages12
JournalPharmaceutical Research
Issue number8
Publication statusPublished - 2012 Aug

Bibliographical note

Funding Information:
This work was supported by a grant from the Korea Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A110879).

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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