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Updated: May 23, 2026
Polyelectrolyte Complex for Heparin Binding Domain Osteogenic Growth Factor Delivery
Published on: August 22, 2016
Bioreducible crosslinked polyelectrolyte complexes for MMP-2 siRNA delivery into human vascular smooth muscle cells
Dokyoung Lee1, Dongkyu Kim, Hyejung Mok
1Severance Integrative Research Institute for Cerebral and Cardiovascular Disease, Yonsei University Health System, 250 Seongsanno, Seodaemun-gu, Seoul, 120-752, South Korea.
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 PEI-DA/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 in MMP-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.
