Synergistic effect between components of mixtures of cationic amphipaths in transfection of primary endothelial cells.
Synergistic effect between components of mixtures of cationic amphipaths in transfection of primary endothelial cells.
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DOI：
10.1021/mp0601291
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发表时间：
2007-04
影响因子：
4.9
通讯作者：
Li Wang;R. Macdonald
中科院分区：
文献类型：
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作者：
Li Wang;R. Macdonald
到目前为止，提高阳离子脂类的转染性的主要途径是合成新型的阳离子两端路径。然而，最近发现，结合两个具有相同头部基团但尾部不同链长的阳离子脂衍生物可以提供另一种通常更好的方法来获得更高的转染率。例如，O-乙基磷脂酰胆碱的中链和长链同系物组合将DNA导入原代人脐动脉内皮细胞(HUAECs)的效率比单独使用这两种化合物的效率高30倍以上。据报道，这种混合物的协同作用并不局限于O-乙基磷脂酰胆碱同系物，其他常见的阳离子两亲性转染剂也表现出这种协同作用；例如，DC-Chol(3beta-[N‘，N’-二甲氨基乙烷)-氨基甲酚]胆固醇、二甲基二十四烷基溴化铵或DMTAP(1，2-二肉豆蔻基-3-三甲基铵-丙烷)与EDOPC在无血清和有血清存在的情况下都显著增加了转染率。此外，将较差的转染剂--二甲基二十八烷基溴化铵--与二甲基二十四烷基溴化铵相结合，可使转染率增加约一个数量级，最大值出现在中间组分。一些混合物缺乏协同作用，如DMTAP和DOTAP(1，2-二油酰基-3-三甲基-丙烷)，在这种情况下，在无血清和有血清存在的情况下，转染率都是组成的线性函数。虽然混合载体增强转染率的机制还不完全清楚，但存在一些具有不同阳离子化合物的最佳混合体系，这表明关注混合物配方可以大大提高阳离子两亲性载体的转染率。
To date, the primary approach to improving the transfection properties of cationic lipids has been the synthesis of new kinds of cationic amphipaths. Recently, however, it was found that combining two cationic lipid derivatives having the same head group but tails of different chain lengths can provide another, and often superior, approach to higher transfection efficiency. For example, the combination of medium-chain and long-chain homologues of O-ethylphosphatidylcholine transfected DNA into primary human umbilical artery endothelial cells (HUAECs) more than 30-fold more efficiently than did either compound separately. Here it is reported that this synergism of mixtures is not limited to O-ethylphosphatidylcholine homologues, but is also exhibited by other common cationic amphipathic transfection reagents; for example, combining DC-Chol (3beta-[N',N'-dimethylaminoethane)-carbamol] cholesterol), dimethylditetradecylammonium bromide, or DMTAP (1,2-dimyristoyl-3-trimethylammonium-propane) with EDOPC increased transfection significantly both in the absence and in the presence of serum. Furthermore, combining a poorer transfection agent-dimethyldioctadecylammonium bromide-with dimethylditetradecylammonium bromide increased transfection by about an order of magnitude with a maximum at an intermediate composition. Lack of synergy occurred with some mixtures, such as DMTAP and DOTAP (1,2-dioleoyl-3-trimethylammonium-propane), in which case transfection activity was a linear function of composition both in the absence and presence of serum. Although the mechanism of enhanced transfection by mixtures is not fully understood, the existence of a number of optimal mixtures with diverse cationic compounds indicates that attention to mixture formulations can lead to greatly improved transfection by cationic amphipathic carriers.