Novel gemini cationic lipids with carbamate groups for gene delivery.
Novel gemini cationic lipids with carbamate groups for gene delivery.
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DOI：
10.1039/c3tb21506g
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发表时间：
2014-05-21
期刊：
影响因子：
--
通讯作者：
Huang L
中科院分区：
文献类型：
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作者：
Zhao YN;Qureshi F;Zhang SB;Cui SH;Wang B;Chen HY;Lv HT;Zhang SF;Huang L
为了获得高效的非病毒载体，合成了一系列在头部基团和疏水尾部之间具有氨基甲酸酯接头的Gemini阳离子脂质。它们具有12、14、16和18个碳原子的烃链作为尾部，分别命名为G12、G14、G16和G18。将这些Gemini阳离子脂质制备成阳离子脂质体，用于理化性质和基因传递的研究。这些Gemini阳离子脂质体的DNA结合能力比它们的单头对应物（分别命名为M12、M14、M16和M18）好得多。在同一系列的脂质体中，结合能力随着尾长的增加而下降。在Hep-2和A549细胞中测试了它们的基因转移能力。它们显示出比它们的单头对应物更高的转染效率，并且在转染效率和细胞毒性方面与商业脂质体、DOTAP和Lipofectamine 2000相当或上级。我们的研究结果令人信服地表明，这些阳离子脂质的基因转移能力取决于烃链的长度。基因转染效率在链长为14时最大，因为G14可以沉默A549细胞中约80%的荧光素酶。细胞摄取结果表明，Gemini脂质递送系统可以非常有效地被细胞内化。因此，Gemini阳离子脂质体可作为人工合成的非病毒基因载体进行进一步的研究。
To obtain efficient non-viral vectors, a series of Gemini cationic lipids with carbamate linkers between headgroups and hydrophobic tails were synthesized. They have the hydrocarbon chains of 12, 14, 16 and 18 carbon atoms as tails, designated as G12, G14, G16 and G18, respectively. These Gemini cationic lipids were prepared into cationic liposomes for the study of the physicochemical properties and gene delivery. The DNA-bonding ability of these Gemini cationic liposomes was much better than their mono-head counterparts (designated as M12, M14, M16 and M18, respectively). In the same series of liposomes, bonding ability declined with an increase in tail length. They were tested for their gene-transferring capabilities in Hep-2 and A549 cells. They showed higher transfection efficiency than their mono-head counterparts and were comparable or superior in transfection efficiency and cytotoxicity to the commercial liposomes, DOTAP and Lipofectamine 2000. Our results convincingly demonstrate that the gene-transferring capabilities of these cationic lipids depended on hydrocarbon chain length. Gene transfection efficiency was maximal at a chain length of 14, as G14 can silence about 80 % of luciferase in A549 cells. Cell uptake results indicate that Gemini lipid delivery systems could be internalised by cells very efficiently. Thus, the Gemini cationic lipids could be used as synthetic non-viral gene delivery carriers for further study.