Pyridinium cationic lipids in gene delivery: A structure-activity correlation study
Pyridinium cationic lipids in gene delivery: A structure-activity correlation study
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DOI：
10.1021/jm0499763
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发表时间：
2004-07-15
影响因子：
7.3
通讯作者：
Balaban, AT
中科院分区：
文献类型：
--
作者：
Ilies, MA;Seitz, WA;Balaban, AT
通过吡喃鎓盐与氨基二醇反应，然后与脂肪酰氯酰化，制备了三个系列的用作非病毒基因递送剂的吡啶鎓阳离子脂质。在这组化合物的基础上，我们进行了全面的结构-活性关系的研究，在水平上的连接，疏水锚，和counterweight，以确定的结构元素，产生最高的转染效率，这种新型的阳离子脂质。结果显示，当与胆固醇以1：1摩尔比配制时，六氟磷酸盐（5AMyr）或氯化物（5DMyr）形式的1-（1，3-二肉豆蔻酰氧基丙-2-基）-2，4，6-三甲基吡啶鎓能够以超过经典的基于DOTAP的制剂的效率和较低的细胞毒性抑制NCl-H23肺癌。随后对其他恶性肿瘤的测试也取得了类似的有希望的结果。
Three series of pyridinium cationic lipids useful as nonviral gene delivery agents were prepared by reaction of pyrylium salts with aminodiols, followed by acylation with fatty acyl chlorides. On the basis of this set of compounds, we undertook a comprehensive structure-activity relationship study at the level of the linker, hydrophobic anchor, and counterion in order to identify the structural elements that generate the highest transfection efficiency for this new type of cationic lipid. The results revealed that when formulated with cholesterol at a 1: 1 molar ratio, the 1-(1,3-dimyristoyloxyprop-2-yl)-2,4,6-trimethylpyridinium, under the form of hexafluorophosphate (5AMyr) or chloride (5DMyr), was able to transfect NCl-H23 lung carcinoma with efficiencies surpassing classic DOTAP-based formulations and with lower cytotoxicity. Subsequent tests on other malignancies yielded similarly promising results.