Effect of non-ionic surfactants on the formation of DNA/emulsion complexes and emulsion-mediated gene transfer
Effect of non-ionic surfactants on the formation of DNA/emulsion complexes and emulsion-mediated gene transfer
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DOI：
10.1023/a:1016480421204
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发表时间：
1996-11-01
影响因子：
3.7
通讯作者：
Liu, DX
中科院分区：
文献类型：
--
作者：
Liu, F;Yang, JP;Liu, DX
目的.研究非离子型表面活性剂在乳剂介导的基因传递中的构效关系。选用Tween、Span、Brij和Pluronic四种不同类型的非离子表面活性剂作为助乳化剂，制备了蓖麻油、二油酰磷脂酰乙醇胺（DOPE）和β-[N-（N '，N'-二甲氨基乙烷）氨甲酰基]胆固醇（DC-Chol）的乳状液。以含荧光素酶cDNA的质粒DNA为报告基因，分析了不同表面活性剂对DNA/乳液复合物形成及转染活性的影响。含有支链聚氧乙烯链作为亲水性头基的非离子表面活性剂比含有一个或不含聚氧乙烯链的表面活性剂更有效地防止形成大的DNA/乳液复合物。除含有Brij 700的乳剂外，所有乳剂制剂在无血清条件下对小鼠BL-6细胞均表现出高的转染活性。然而，在血清存在下，每种制剂的转染活性显著变化。含有Tween、Brij 72、pluronic F68和F127的乳剂在208血清存在下表现出增加的转染细胞活性。与含有Span的乳液相反，Birj的长链聚氧乙烯显示出降低的转染活性。DNA/乳剂复合物的粒径及其对细胞的抑制能力取决于制剂中非离子表面活性剂的浓度。乳液中非离子表面活性剂的亲水头基的结构在确定DNA分子如何与乳液相互作用以及DNA在细胞内转移的程度方面是重要的。
Purpose. To study the structure-function relationship of non-ionic surfactants in emulsion-mediated gene delivery.Methods. Four different types of non-ionic surfactants including Tween, Span, Brij and pluronic copolymers were used as co-emulsifiers far preparation of emulsions composed of Castor oil, dioleoylphosphatidylethanolamine (DOPE) and (3) beta[N-(N', N'-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol). The effect of different surfactants on the formation of DNA/emulsion complexes and transfection activity were analyzed using plasmid DNA containing luciferase cDNA as a reporter gene.Results. Non-ionic surfactants containing branched polyoxyethylene chains as the hydrophilic head group were more effective in preventing the formation of large DNA/emulsion complexes than those containing one or no polyoxyethylene chain. All emulsion formulations except those containing Brij 700 exhibited high activity in transfecting mouse BL-6 cells in the absence of serum. In the presence of serum, however, transfection activity of each formulation varied significantly. Emulsions containing Tween, Brij 72, pluronic F68 and F127 demonstrated increased activity in transfecting cells in the presence of 208 serum. In contrast to emulsions containing Span, long chain polyoxyethylene of Birj showed decreased transfection activity. The particle size of the DNA/emulsion complexes and their ability to transfect cells are dependent on the concentration of non-ionic surfactant in the formulationConclusions. The structure of the hydrophilic head group of the nonionic surfactants in the emulsion is important in determining how DNA molecules interact with emulsions and the extent to which DNA is transferred inside the cell.