Hyaluronic acid-polyethyleneimine conjugate for target specific intracellular delivery of siRNA

A novel target specific small interfering RNA (siRNA) delivery system was successfully developed using I polyethyleneimine (PEI)-hyaluronic acid (HA) conjugate. Anti-PGL3-Luc siRNA was used as a model system suppressing the PGL3-Luc gene expression. The siRNA/PEI-HA complex with an average size of ca.21 nm appeared to be formed by electrostatic interaction between the negatively charged siRNA and the positively charged PEI of PEI-HA conjugate. The cytotoxicity of siRNA/PEI-HA complex to B16F1 cells was lower than that of siRNA/PEI complex according to the MTTassay. When B16F1 and HEK-293 cells were treated with fluorescein isothiocyanate (FITC) labeled siRNA/PEI-HA complex, B16F1 cells, with a lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), showed higher green fluorescent intensity than HEK-293 cells because of the HA receptor mediated endocytosis of the complex. Accordingly, the PGL3-Luc gene silencing of anti-PGL3-Luc siRNA/PEI-HA complex was more efficient in B16F1 cells than in HEK-293 cells. In addition, the inhibited PGL3-Luc gene silencing effect in the presence of free HA in the transfection medium revealed that siRNA/HA-PEI complex was selectively taken up to B16F1 cells via HA receptor mediated endocytosis. All these results demonstrated that the intracellular delivery of anti-PGL3-Luc siRNA/PEI-HA complex could be facilitated by the HA receptor mediated endocytosis. (c) 2008 Wiley Periodicals, Inc.
Publisher
Wiley-Blackwell
Issue Date
2008-07
Language
ENG
Keywords

POLYELECTROLYTE COMPLEX MICELLES; SUSTAINED-RELEASE FORMULATION; MEDIATED GENE DELIVERY; IN-VIVO; RNA INTERFERENCE; SODIUM HYALURONATE; GROWTH; RECEPTOR; CELLS; PROLIFERATION

Citation

BIOPOLYMERS, v.89, no.7, pp.635 - 642

ISSN
0006-3525
DOI
10.1002/bip.20978
URI
http://hdl.handle.net/10203/13285
Appears in Collection
BS-Journal Papers(저널논문)
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