Amidine-bearing lipoplex targeting to hepatocyte cells  

作　　者：Yasuya Kudo Kazunori Koiwai Kazuhiro Shimizu Shota Kusuki Mina Sakuragi Naohiko Shimada Yoichi Takeda Kazuo Sakurai 

机构地区：[1]Department of Chemical Process & Environments,Faculty of Environmental Engineering,The University of Kitakyushu,1-1,Hibikino,Wakamatsu-ku,Kitakyushu,Fukuoka 808-0135,Japan [2]TERUMO Corporation R & D Center,1500 Inokuchi,Nakai-machi,Ashigarakami-gun Kanagawa 259-0151,Japan

出　　处：《Chinese Chemical Letters》2008年第9期1115-1118,共4页中国化学快报（英文版）

基　　金：SORST of JST and a Grant-in-Aid for Scientific Research(No.16350068 and 16655048);SAXS was performed at SPring-8 BL40B2(No.2006A1510).

摘　　要：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 cellulartargeting ability through the receptors for oligosaccharide.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 cellulartargeting ability through the receptors for oligosaccharide.

关 键 词：Gene theraphy AMIDINE GALACTOSYLCERAMIDE TARGETING 

分 类 号：R346[医药卫生—基础医学]