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

✍ Scribed by Ge Jiang; Kitae Park; Jiseok Kim; Ki Su Kim; Eun Ju Oh; Hyungu Kang; Su-Eun Han; Yu-Kyoung Oh; Tae Gwan Park; Sei Kwang Hahn

Publisher
Wiley (John Wiley & Sons)
Year
2008
Tongue
English
Weight
286 KB
Volume
89
Category
Article
ISSN
0006-3525

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✦ Synopsis

Abstract

A novel target specific small interfering RNA (siRNA) delivery system was successfully developed using 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 MTT assay. 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. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 635–642, 2008.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at [email protected]

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