Ju Jia, Huan Meng-Lei, Wan Ning, Hou Yi-Lin, Ma Xi-Xi, Jia Yi-Yang, Li Chen, Zhou Si-Yuan, Zhang Bang-Le
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China; Department of Pharmacy, School of Stomatology, Fourth Military Medical University, Xi'an 710032, China.
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
Bioorg Med Chem Lett. 2016 May 15;26(10):2401-2407. doi: 10.1016/j.bmcl.2016.04.007. Epub 2016 Apr 6.
Cholesterol derivatives M1-M6 as synthetic cationic lipids were designed and the biological evaluation of the cationic liposomes based on them as non-viral gene delivery vectors were described. Plasmid pEGFP-N1, used as model gene, was transferred into 293T cells by cationic liposomes formed with M1-M6 and transfection efficiency and GFP expression were tested. Cationic liposomes prepared with cationic lipids M1-M6 exhibited good transfection activity, and the transfection activity was parallel (M2 and M4) or superior (M1 and M6) to that of DC-Chol derived from the same backbone. Among them, the transfection efficiency of cationic lipid M6 was parallel to that of the commercially available Lipofectamine2000. The optimal formulation of M1 and M6 were found to be at a mol ratio of 1:0.5 for cationic lipid/DOPE, and at a N/P charge mol ratio of 3:1 for liposome/DNA. Under optimized conditions, the efficiency of M1 and M6 is greater than that of all the tested commercial liposomes DC-Chol and Lipofectamine2000, even in the presence of serum. The results indicated that M1 and M6 exhibited low cytotoxicity, good serum compatibility and efficient transfection performance, having the potential of being excellent non-viral vectors for gene delivery.
设计了胆固醇衍生物M1 - M6作为合成阳离子脂质，并描述了基于它们的阳离子脂质体作为非病毒基因传递载体的生物学评价。用作模型基因的质粒pEGFP - N1通过由M1 - M6形成的阳离子脂质体转入293T细胞，并测试了转染效率和绿色荧光蛋白（GFP）表达。用阳离子脂质M1 - M6制备的阳离子脂质体表现出良好的转染活性，且转染活性与源自相同骨架的DC - Chol相当（M2和M4）或更优（M1和M6）。其中，阳离子脂质M6的转染效率与市售的Lipofectamine2000相当。发现M1和M6的最佳配方为阳离子脂质/二油酰磷脂酰乙醇胺（DOPE）的摩尔比为1:0.5，脂质体/DNA的氮/磷电荷摩尔比为3:1。在优化条件下，即使在有血清存在的情况下，M1和M6的效率也高于所有测试的商业脂质体DC - Chol和Lipofectamine2000。结果表明，M1和M6具有低细胞毒性、良好的血清相容性和高效的转染性能，有潜力成为优异的非病毒基因传递载体。
