Asialoglycoprotein receptor-mediated gene transfer using novel galactosylated cationic liposomes

被引：146

作者：

Kawakami, S ^{[1
]}

Yamashita, F ^{[1
]}

Nishikawa, M ^{[1
]}

Takakura, Y ^{[1
]}

Hashida, M ^{[1
]}

机构：

[1] Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Drug Delivery Res, Sakyo Ku, Kyoto 6068501, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1998年 / 252卷 / 01期

关键词：

D O I：

10.1006/bbrc.1998.9602

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We synthesized three novel galactosylated cholesterol derivatives, cholesten-5-yloxy-N- (4-((1-imino-c-beta-D-thiogalactosyl-ethyl) amino)butyl)formamide (GalC4-Chol) and its ethyl formamide and hexyl formamide analogues (Gal-C2-Chol, Gal-C6-Chol), to prepare liposomal gene carriers possessing the cationic charge necessary for plasmid DNA binding and galactose residues as a targetable ligand for liver parenchymal cells. Liposome/DNA complexes prepared with these lipids showed low cytotoxicity in human hepatoma HepG2 cells. Gal-C4-Chol/DC-Chol/DOPE(3: 3:4) liposomes, consisting of 3:3:4 mixtures of Gal-C4-Chol, 3 beta[N',N',N',-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol), and dioleoylphosphatidylethanolamine (DOPE), showed higher transfection activity and [P-32]DNA uptake than DC-Chol/DOPE(6:4) liposomes. The presence of 20 mM galactose significantly inhibited both transfection efficiency and uptake of DNA of Gal-C4-Chol/DC-Chol/DOPE (3:3:4) and Gal-C4-Chol/DOPE(6:4) liposomes, but not those of DC-Chol/ DOPE(6:4) liposomes. These results indicate that the liposome/DNA complexes prepared using novel galactosylated cholesterol derivatives are efficiently recognized by asialoglycoprotein receptors and internalized and lead to gene expression. In addition, we found that the galactosylated cholesterol derivative with a longer spacer showed higher transfection activity. (C) 1998 Academic Press.

引用

页码：78 / 83

页数：6

共 22 条

[1]

AKAMATSU K, 1998, IN PRESS J DRUG TARG

[2] BINDING OF BIOTINATED-LIPOSOMES TO STREPTAVIDIN IS INFLUENCED BY LIPOSOME COMPOSITION [J].

CORLEY, P ;

LOUGHREY, HC .

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1994, 1195 (01) :149-156

[3]

FUJITA T, 1992, J PHARMACOL EXP THER, V263, P971

[4] A NOVEL CATIONIC LIPOSOME REAGENT FOR EFFICIENT TRANSFECTION OF MAMMALIAN-CELLS [J].

GAO, X ;

HUANG, L .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 179 (01) :280-285

[5] SUCCESSFUL EX-VIVO GENE-THERAPY DIRECTED TO LIVER IN A PATIENT WITH FAMILIAL HYPERCHOLESTEROLEMIA [J].

GROSSMAN, M ;

RAPER, SE ;

KOZARSKY, K ;

STEIN, EA ;

ENGELHARDT, JF ;

MULLER, D ;

LUPIEN, PJ ;

WILSON, JM .

NATURE GENETICS, 1994, 6 (04) :335-341

[6] RECEPTOR-MEDIATED TRANSFER OF PSV2CAT DNA TO A HUMAN HEPATOBLASTOMA CELL-LINE HEPG2 USING ASIALOFETUIN-LABELED CATIONIC LIPOSOMES [J].

HARA, T ;

ARAMAKI, Y ;

TAKADA, S ;

KOIKE, K ;

TSUCHIYA, S .

GENE, 1995, 159 (02) :167-174

[7]

Hara T, 1995, GENE THER, V2, P784

[8] Effects of fusogenic and DNA-binding amphiphilic compounds on the receptor-mediated gene transfer into hepatic cells by asialofetuin-labeled liposomes [J].

Hara, T ;

Kuwasawa, H ;

Aramaki, Y ;

Takada, S ;

Koike, K ;

Ishidate, K ;

Kato, H ;

Tsuchiya, S .

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1996, 1278 (01) :51-58

[9] Development and pharmacokinetics of galactosylated poly-L-glutamic acid as a biodegradable carrier for liver-specific drug delivery [J].

Hirabayashi, H ;

Nishikawa, M ;

Takakura, Y ;

Hashida, M .

PHARMACEUTICAL RESEARCH, 1996, 13 (06) :880-884

[10] Sterically stabilized Anti-HER2 immunoliposomes: Design and targeting to human breast cancer cells in vitro [J].

Kirpotin, D ;

Park, JW ;

Hong, K ;

Zalipsky, S ;

Li, WL ;

Carter, P ;

Benz, CC ;

Papahadjopoulos, D .

BIOCHEMISTRY, 1997, 36 (01) :66-75

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