Design, synthesis and gene delivery efficiency of novel oligo-arginine-linked PEG-lipids: Effect of oligo-arginine length

被引:21
作者
Furuhata, Masahiko
Kawakami, Hiroko
Toma, Kazunori
Hattori, Yoshiyuki
Maitani, Yoshie
机构
[1] Hoshi Univ, Inst Med Chem, Shinagawa Ku, Tokyo 1428501, Japan
[2] Noguchi Inst, Itabashi Ku, Tokyo 1730003, Japan
关键词
cell penetrating peptides; oligo-arginine; gene delivery;
D O I
10.1016/j.ijpharm.2006.02.041
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The design, synthesis, and evaluation of in vitro gene delivery efficacy of a novel series of oligo-Arg-lipid conjugates are described. 3,5-Bis(dodecyloxy)benzamide (BDB) was employed as the lipid component, and a poly(ethylene glycol) (PEG) spacer was introduced between the C-terminal of oligo-Arg and the amide group of BDB. Four derivatives with various oligo-Arg lengths (ArgN-PEG-BDB; N=4, 6, 8, 10: the number of arginine residues) were prepared, and the effect of oligo-Arg length on the gene transfection was investigated in HeLa cells. Transfection efficiency increased as the number of arginine residues increased. Arg10-PEG-BDB showed the highest transfection efficiency, without severe toxicity to cells. These findings well corresponded to the cellular association of the Arg-PEG-BDB/DNA complex determined by flow cytometry. Even in the presence of serum, Arg10-PEG-BDB achieved appreciable cellular association and attained high gene expression. Thus, Arg10-PEG-BDB is potentially a simple and useful gene delivery tool, because one need only to mix it with plasmid DNA and apply the complexes to the cells even in a serum-containing medium. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:109 / 116
页数:8
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