Generation of highly potent nonviral gene vectors by complexation of lipoplexes and transferrin-bearing fusogenic polymer-modified liposomes in aqueous glucose solution
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- 作者：Naoki Sakaguchi ; Chie Kojima ; Atsushi Harada ; Kazunori Koiwai ; Kazuhiro Shimizu ; Nobuhiko Emi ; Kenji Kono
- 关键词：Nonviral vector ; Liposome ; Lipoplex ; Gene therapy ; Transferrin ; Fusion
- 刊名：Biomaterials
- 出版年：2008
- 出版时间：March 2008
- 年：2008
- 卷：29
- 期：9
- 页码：1262-1272
- 全文大小：1584 K
文摘
We reported previously that complexation of lipoplexes containing 3,5-dipentadecyloxybenzamidine (TRX-20) and transferrin-bearing succinylated poly(glycidol) (SucPG)-modified liposome, which becomes fusogenic under weakly acidic conditions, might produce gene carriers with high transfection activity. For the present study, we prepared the lipoplex–SucPG-modified liposome complexes by mixing them either in phosphate-buffered saline or in an aqueous 5 % glucose solution. The complexes prepared in phosphate-buffered saline have large particles of more than 800 nm, whereas the complexes prepared in the glucose solution were remarkably small: 200–300 nm. The small complexes were taken up more effectively by HeLa cells, and their transfection was induced more efficiently than the large complexes'. In addition, the small complexes achieved cellular transfection more efficiently in the presence of serum than in the absence of serum, without marked cytotoxicity. Considering that their affinity to the cell is based on ligand–receptor interaction, the small complexes are highly promising as a safe vector with high transfection activity and high target cell specificity.