Max Planck Institute of Colloids and Interfaces, Science Park Potsdam-Golm, Potsdam, Germany.
Chemphyschem. 2011 Aug 22;12(12):2328-37. doi: 10.1002/cphc.201100065. Epub 2011 Jun 14.
Cationic liposome/DNA complexes can be used as nonviral vectors for direct delivery of DNA-based biopharmaceuticals to damaged cells and tissues. To obtain more effective and safer liposome-based gene transfection systems, two cationic lipids with identical head groups but different chain structures are investigated with respect to their in vitro gene-transfer activity, their cell-damaging characteristics, and their physicochemical properties. The gene-transfer activities of the two lipids are very different. Differential scanning calorimetry and synchrotron small- and wide-angle X-ray scattering give valuable structural insight. A subgel-like structure with high packing density and high phase-transition temperature from gel to liquid-crystalline state are found for lipid 7 (N'-2-[(2,6-diamino-1-oxohexyl)amino]ethyl-2,N-bis(hexadecyl)propanediamide) containing two saturated chains. Additionally, an ordered head-group lattice based on formation of a hydrogen-bond network is present. In contrast, lipid 8 (N'-2-[(2,6-diamino-1-oxohexyl)amino]ethyl-2-hexadecyl-N-[(9Z)-octadec-9-enyl]propanediamide) with one unsaturated and one saturated chain shows a lower phase-transition temperature and a reduced packing density. These properties enhance incorporation of the helper lipid cholesterol needed for gene transfection. Both lipids, either pure or in mixtures with cholesterol, form lamellar phases, which are preserved after addition of DNA. However, the system separates into phases containing DNA and phases without DNA. On increasing the temperature, DNA is released and only a lipid phase without intercalated DNA strands is observed. The conversion temperatures are very different in the two systems studied. The important parameter seems to be the charge density of the lipid membranes, which is a result of different solubility of cholesterol in the two lipid membranes. Therefore, different binding affinities of the DNA to the lipid mixtures are achieved.
阳离子脂质体/DNA 复合物可用作将基于 DNA 的生物制药直接递送至受损细胞和组织的非病毒载体。为了获得更有效和更安全的基于脂质体的基因转染系统，研究了两种具有相同头基但不同链结构的阳离子脂质，以研究它们的体外基因转移活性、细胞损伤特性和物理化学性质。这两种脂质的基因转移活性有很大的不同。差示扫描量热法和同步加速器小角和广角 X 射线散射给出了有价值的结构见解。发现含有两条饱和链的脂质 7（N'-2-[(2,6-二氨基-1-氧代己基)氨基]乙基-2，N-双（十六烷基）丙二酰胺）具有类似亚凝胶的结构，具有高密度堆积和从凝胶态到液晶态的高相变温度。此外，还存在基于氢键网络形成的有序头基晶格。相比之下，含有一条不饱和链和一条饱和链的脂质 8（N'-2-[(2,6-二氨基-1-氧代己基)氨基]乙基-2-十六烷基-N-[(9Z)-十八-9-烯基]丙二酰胺）具有较低的相变温度和较低的堆积密度。这些性质增强了基因转染所需的辅助脂质胆固醇的掺入。两种脂质，无论是纯的还是与胆固醇的混合物，都形成层状相，在加入 DNA 后仍保持不变。然而，该系统会分离成含有 DNA 的相和不含 DNA 的相。随着温度的升高，DNA 被释放，并且只观察到没有插入 DNA 链的脂质相。在所研究的两个系统中，转换温度非常不同。重要的参数似乎是脂质膜的电荷密度，这是由于胆固醇在两种脂质膜中的不同溶解度所致。因此，实现了 DNA 与脂质混合物的不同结合亲和力。
