Interaction of Cationic Lipid/DNA Complexes with Model Membranes As Determined by Neutron Reflectivity
Interaction of Cationic Lipid/DNA Complexes with Model Membranes As Determined by Neutron Reflectivity
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DOI：
10.1021/la802847h
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发表时间：
2009-04-07
期刊：
影响因子：
3.9
通讯作者：
Lawrence, M. J.
中科院分区：
文献类型：
--
作者：
Callow, P.;Fragneto, G.;Lawrence, M. J.
通过使用阳离子脂质/DNA“脂质复合物”，可以有效地工程化用于基因治疗目的的DNA转染细胞，尽管这些复合物的转染效率对所包括的中性“辅助”脂质敏感。在这里，中子反射率已被用来调查的辅助脂质的作用，这些lipoplexes与模型膜主要由两性离子脂质1，2-二肉豆蔻酰磷脂酰胆碱（DMPQ）以及10摩尔%的1，2-二棕榈酰磷脂酰丝氨酸（DPPS）的相互作用过程中存在。二甲基双十八烷基溴化铵（DDAB）囊泡与两种不同的辅助脂质，1，2-二油酰基-sn-甘油-3-磷脂酰乙醇胺（DOPE）和胆固醇，并与1：1的电荷比的DNA复合。这些复合物与支持磷脂双层的相互作用进行了测定。发现含DOPE的脂质复合物与模型细胞膜的相互作用比含胆固醇的更快，并且发现含有任一中性辅助脂质的复合物与DDAB单独存在时的相互作用更快。脂质复合物和模型膜之间的相互作用的特征在于通过膜和溶液中的脂质/DNA聚集体之间的脂质交换;模型细胞膜表面上的（额外的）脂质沉积不明显。
Transfection of cells by DNA for the purposes of gene therapy can be effectively engineered through the use of cationic lipid/DNA "lipoplexes", although the transfection efficiency of these complexes is sensitive to the neutral "helper" lipid included. Here, neutron reflectivity has been used to investigate the role of the helper lipid present during the interaction of these lipoplexes with model membranes composed primarily of zwitterionic lipid 1,2-dimyristoylphosphatidylcholine (DMPQ together with 10 mol % 1,2-dipalmitoylphosphatidylserine (DPPS). Dimethyldioctadecylammonium bromide (DDAB) vesicles were formed with two different helper lipids, 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE) and cholesterol, and complexed with a 1: 1 charge ratio of DNA. The interaction of these complexes with the supported phospholipid bilayer was determined. DOPE-containing lipoplexes were found to interact faster with the model cell membrane than those containing cholesterol, and complexes containing either of the neutral helper lipids were found to interact faster than when DDAB alone was present. The interaction between the lipoplexes and the model membrane was characterized by an exchange of lipid between the membrane and the lipid/DNA aggregates in solution; the deposition of (additional) lipid on the surface of the model cell membrane was not apparent.