Citation: Yasuya Kudo, Kazunori Koiwai, Kazuhiro Shimizu, Shota Kusuki, Mina Sakuragi, Naohiko Shimada, Yoichi Takeda, Kazuo Sakurai. Amidine-bearing lipoplex targeting to hepatocyte cells[J]. Chinese Chemical Letters, ;2008, 19(9): 1115-1118. doi: 10.1016/j.cclet.2008.06.001 shu

Amidine-bearing lipoplex targeting to hepatocyte cells

a Department of Chemical Process & Environments, Faculty of Environmental Engineering, The University of Kitakyushu, 1-1, Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan;
b TERUMO Corporation R & D Center, 1500 lnokuchi, Nakai-machi, Ashigarakami-gun Kanagawa 259-0151, Japan

Received Date: 7 December 2007

Fund Project: This work is finically supported by SORST of JST and a Grant-in-Aid for Scientific Research (No. 16350068 and 16655048). SAXS was performed at SPring-8 BL40B2 (2006A1510)

A lipoplex (i.e., pDNA^#1/lipid complex and transfection reagent for pDNA delivery) containing galactosylceramide (GalCer) and an amidine-bearing lipid (TRX) was examined whether the bound pDNA was specifically ingested by hepatocyte via asialoglycoprotein receptor (ASGPR) and then expressed protein. Gel electrophoresis and small-angle X-ray scattering (SAXS) confirmed that the TRX-GalCer liposome^#2 complexed with pDNA and the resultant lipoplex took a hexagonally packed inverted cylinder structure when the GalCer composition was less than 20 wt.% of the total lipid. When the lipoplex carrying pGL3 (luciferase-cording pDNA) was administrated to HepG2, the luciferase activity was increased with increasing the GalCer composition until it reached 3 wt.% and then decreased upon further addition of GalCer. When we added galactose itself as a competitor, the luciferase activity was decreased, while glucose did not show such decrease, suggesting that HepG2 ingested the lipoplex via ASGPR-mediated endocytosis. This paper indicated that the hexagonally packed inverted cylinder structures of lipoplex may not always provide excellent transfection and presented a possibility that the TRX lipoplex^#3 can obtain a cellular-targeting ability through the receptors for oligosaccharide.
- Gene theraphy,
- Amidine,
- Galactosyleeramide,
- Targeting
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