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 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.
Jiang
Ge
G
Department of Material Science and Engineering, Pohang University of Science and Technology (POSTECH), San 31, Hyoja-dong, Nam-gu, Pohang, 790-784, Korea.
Park
Kitae
K
Kim
Jiseok
J
Kim
Ki Su
KS
Oh
Eun Ju
EJ
Kang
Hyungu
H
Han
Su-Eun
SE
Oh
Yu-Kyoung
YK
Park
Tae Gwan
TG
Kwang Hahn
Sei
S
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
D034741:RNA, Small Interfering; D011094:Polyethyleneimine; D006820:Hyaluronic Acid; D016650:Fluorescein-5-isothiocyanate