title: Hyaluronic acid-polyethyleneimine conjugate for target specific intracellular delivery of siRNA.
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.
authors.affiliation: Department of Material Science and Engineering, Pohang University of Science and Technology (POSTECH), San 31, Hyoja-dong, Nam-gu, Pohang, 790-784, Korea.
authors.forename: Ge
authors.initials: G
authors.lastname: Jiang
authors.forename: Kitae
authors.initials: K
authors.lastname: Park
authors.forename: Jiseok
authors.initials: J
authors.lastname: Kim
authors.forename: Ki Su
authors.initials: KS
authors.lastname: Kim
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Oh
authors.forename: Hyungu
authors.initials: H
authors.lastname: Kang
authors.forename: Su-Eun
authors.initials: SE
authors.lastname: Han
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
authors.forename: Tae Gwan
authors.initials: TG
authors.lastname: Park
authors.forename: Sei
authors.initials: S
authors.lastname: Kwang Hahn
mesh_terms: D002460:Cell Line; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects; D018014:Gene Transfer Techniques; D006820:Hyaluronic Acid / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D018625:Microscopy, Atomic Force; D015394:Molecular Structure; D011094:Polyethyleneimine / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D034741:RNA, Small Interfering; D011094:Polyethyleneimine; D006820:Hyaluronic Acid; D016650:Fluorescein-5-isothiocyanate