Novel receptor-mediated gene delivery system comprising plasmid/protamine/sugar-containing polyanion ternary complex

被引：59
作者：
Maruyama, K
Iwasaki, F
Takizawa, T
Yanagie, H
Niidome, T
Yamada, E
Ito, T
Koyama, Y [1 ]
机构：
[1] Otsuma Womens Univ, Dept Text Sci, Chiyoda Ku, Tokyo 1028357, Japan
[2] Teikyo Univ, Fac Pharmaceut Sci, Sagamiko, Kanagawa 1990195, Japan
[3] Univ Tokyo, Adv Sci & Technol Res Ctr, Meguro Ku, Tokyo 1530041, Japan
[4] Nagasaki Univ, Fac Engn, Nagasaki 8528521, Japan
来源：
BIOMATERIALS | 2004年 / 25卷 / 16期
关键词：
gene therapy protamine; polyethylene glycol; hepatocyte; polyion complex;
D O I：
10.1016/j.biomaterials.2003.10.004
中图分类号：
R318 [生物医学工程];
学科分类号：
0831 ;
摘要：
Poly(ethylene glycol) (PEG) derivative having both carboxylic acid-, and lactose-side chains (Lac-PEG-C) deposited onto the surface of DNA/protamine (PRT) complex, and the self-assembled ternary complex was obtained. The diameter of the complexes was 180-200 nm, and they showed good size stability even in the high ionic strength solutions. Lac-PEG-C coating reduced their surface electric potential, and effectively avoided the albumin-induced aggregation. DNA/PRT/Lac-PEG-C complex did not coagulate the red blood cells, and their cytotoxicity evaluated by WST-1 was very low. Lac-PEG-C added to the plasmid/PRT complex prior to the incubation with HepG2 cells extremely enhanced the gene-expression, and by the plasmid/PRT/Lac-PEG-C complex prepared at 1:1.5:8 in weight, 56-fold higher expression of luciferase than that without Lac-PEG-C was observed. The treatment with asialofetuin or phenylarsine oxide evidently interfered with the gene-expression. The high gene expression by the plasmid/PRT/Lac-PEG-C ternary complex on the hepatocyte would be attributed to the asialoglycoprotein receptor-mediated endocytosis. (C) 2003 Elsevier Ltd. All rights reserved.
引用
收藏
页码：3267 / 3273
页数：7
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