Novel pH-sensitive cationic lipids with linear ortho ester linkers for gene delivery.
Novel pH-sensitive cationic lipids with linear ortho ester linkers for gene delivery.
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DOI：
10.1016/j.ejmech.2012.03.013
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发表时间：
2012-06
影响因子：
6.7
通讯作者：
Guo X
中科院分区：
文献类型：
--
作者：
Chen H;Zhang H;Thor D;Rahimian R;Guo X
在努力开发pH敏感的lipoplexes有效的基因传递，我们报告了三种新的阳离子脂质含有线性原酸酯接头，共轭物的头基（I型）或一个烃链（II型）与其余的脂质分子。阳离子脂质携带碘离子或氯离子。与我们先前报道的环状原酸酯连接体相比，线性原酸酯连接体促进了阳离子脂质体和具有不同辅助脂质的脂质复合物的构建。氯离子不仅促进脂质体构建过程中脂质膜的水化，而且还增强了脂质复合物中原酸酯连接基的水解。在内体pH 5.5下孵育后，I型脂质复合物聚集并使内体模拟模型脂质体不稳定，但II型脂质复合物不。辅助脂质（DOPE或胆固醇）的lipoplexes增强的pH值敏感性的I型lipoplexes。在CV-1细胞（猴肾成纤维细胞）中，I型基于原酸酯的脂质复合物，特别是具有氯离子的脂质复合物，与由DOTAP组成的pH不敏感的对应物相比，显著提高了基因转染效率，在某些情况下提高了100倍以上。基于原酸酯的脂质体的基因转染效率与其响应于内体pH 5.5的聚集和膜不稳定的速率密切相关。
In an effort to develop pH-sensitive lipoplexes for efficient gene delivery, we report three novel cationic lipids containing a linear ortho ester linker that conjugates either the headgroup (Type I) or one hydrocarbon chain (Type II) with the rest of the lipid molecule. The cationic lipids carry either an iodide or a chloride counterion. Compared to our previously reported cyclic ortho ester linker, the linear ortho ester linker facilitated the construction of cationic liposomes and lipoplexes with different helper lipids. The chloride counterion not only facilitated the hydration of the lipid films during liposome construction, but also enhanced the hydrolysis of the ortho ester linker in the lipoplexes. After incubation at endosomal pH 5.5, the Type I lipoplexes aggregated and destabilized the endosome-mimicking model liposomes, but not the Type II lipoplexes. The helper lipids (DOPE or cholesterol) of the lipoplexes enhanced the pH-sensitivity of the Type I lipoplexes. In CV-1 cells (monkey kidney fibroblast), the Type I ortho ester-based lipoplexes, especially those with the chloride counterion, significantly improved the gene transfection efficiency, in some cases by more than 100 fold, compared to their pH-insensitive counterparts consisting of DOTAP. The gene transfection efficiency of the ortho ester-based lipoplexes was well correlated with their rate of aggregation and membrane destabilization in response to the endosomal pH 5.5.
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DOI：
10.1006/bbrc.1995.2838
发表时间：
1995-12-26
影响因子：
3.1
作者：
Huang, L;Farhood, H;Barsoum, J
通讯作者：
Barsoum, J
影响因子：
7.3
作者：
Chen, Haigan;Zhang, Huizhen;Guo, Xin
通讯作者：
Guo, Xin
影响因子：
1.8
作者：
AHRLAND, S
通讯作者：
AHRLAND, S
DOI：
10.1002/cber.19610940238
发表时间：
1961-01-01
期刊：
CHEMISCHE BERICHTE-RECUEIL
影响因子：
--
作者：
GROSS, H;RIECHE, A
通讯作者：
RIECHE, A
影响因子：
2.1
作者：
Deslongchamps, P;Dory, YL;Li, SG
通讯作者：
Li, SG