Enhancement of transfection activity of lipoplexes by complexation with transferrin-bearing fusogenic polymer-modified liposomes.
Enhancement of transfection activity of lipoplexes by complexation with transferrin-bearing fusogenic polymer-modified liposomes.
复制标题
DOI：
10.1016/j.ijpharm.2006.06.015
复制
发表时间：
2006-11
影响因子：
5.8
通讯作者：
Naoki Sakaguchi;C. Kojima;Atsushi Harada;Kazunori Koiwai;K. Shimizu;N. Emi;K. Kono
中科院分区：
文献类型：
--
作者：
Naoki Sakaguchi;C. Kojima;Atsushi Harada;Kazunori Koiwai;K. Shimizu;N. Emi;K. Kono
我们以前开发了含有3-β-(N-(N‘，N’-二甲氨基乙烷)氨基甲酰基)胆固醇(DC-CHOL)和琥珀酸化聚缩水甘油修饰脂质体的脂合物，它在弱酸性条件下可以融合，作为一种新的基因递送系统。本研究探讨了脂复合物结构--阳离子脂类的类型和阳离子脂类/DNA电荷比--对这些复合体的转染活性的影响。分别用3种不同极性基团的阳离子脂类：DC-CHOL、N-[1-(2，3-二油酰氧基)丙基]-N，N，N-三甲基甲基硫酸铵(DOTAP)和带有二甲氨基、三甲基氨基和苯甲酰胺基的3，5-二十五烷氧基苯甲酰胺(TRX-20)制备了脂合物。与SucPG修饰的转铁蛋白脂质体的络合作用不同地影响了这些脂联体的转染活性。在这些脂联体中，TRX-20脂联体与SucPG修饰的脂质体络合后显示出最显著的转染活性增强。脂复合体的阳离子脂/DNA电荷比以及与脂复合体结合的转铁蛋白修饰的脂质体的量也影响了所得到的复合体的转染活性。通过对这些因子的调节，获得了高效的基因载体。
We previously developed complexes of lipoplexes containing 3β-(N-(N′,N′-dimethylaminoethane)carbamoyl)cholesterol (DC-chol) and succinylated poly(glycidol)-modified liposome, which becomes fusogenic under weakly acidic condition, for use as a novel gene delivery system. This study explored the effect of lipoplex structures – the type of cationic lipid and cationic lipid/DNA charge ratio – on the transfection activity of those complexes. Three types of cationic lipid with different polar groups were used for the preparation of lipoplexes: DC-chol, N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate (DOTAP), and 3,5-dipentadecyloxybenzamidine (TRX-20) with dimethylamino group, trimethylammonium group, and benzamidine group, respectively. Complexation with the SucPG-modified transferrin-bearing liposomes affected transfection activity of these lipoplexes differently. The TRX-20 lipoplexes exhibited the most marked enhancement of transfection activity upon complexation with the SucPG-modified liposomes among these lipoplexes. The cationic lipid/DNA charge ratio of the lipoplex and the amount of the transferrin-bearing SucPG-modified liposomes associated to the lipoplex also affected the transfection activity of the resultant complexes. Highly potent gene vectors were obtained by adjusting these factors.