Lipid phase control of DNA delivery
Lipid phase control of DNA delivery
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DOI：
10.1021/bc050226x
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发表时间：
2005-11-01
影响因子：
4.7
通讯作者：
MacDonald, RC
中科院分区：
文献类型：
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作者：
Koynova, R;Wang, L;MacDonald, RC
阳离子脂质与聚阴离子DNA形成纳米级复合物（脂质复合物），并可用于将DNA递送至细胞进行转染。在这里，我们报告这些DNA载体的传递效率和介晶相，它们形成时与阴离子膜脂质相互作用之间的相关性。具体地，当与阴离子脂质混合时，作为特别有效的DNA载体的制剂形成具有最高负界面曲率的相，而不太有效的制剂形成具有较低曲率的相。因此，与细胞脂质相互作用后的载体脂质/DNA复合物的结构演变被建议作为脂质介导的DNA递送的控制因素。推导出优化脂质体转染的策略。发现高效lipoplex制剂DOTAP/DOPE的行为符合该“效率公式”。
Cationic lipids form nanoscale complexes (lipoplexes) with polyanionic DNA and can be utilized to deliver DNA to cells for transfection. Here we report the correlation between delivery efficiency of these DNA carriers and the mesomorphic phases they form when interacting with anionic membrane lipids. Specifically, formulations that are particularly effective DNA carriers form phases of highest negative interfacial curvature when mixed with anionic lipids, whereas less effective formulations form phases of lower curvature. Structural evolution of the carrier lipid/DNA complexes upon interaction with cellular lipids is hence suggested as a controlling factor in lipid-mediated DNA delivery. A strategy for optimizing lipofection is deduced. The behavior of a highly effective lipoplex formulation, DOTAP/DOPE, is found to conform to this "efficiency formula".