Interactions of Cationic Lipids with DNA: A Structural Approach (original) (raw)
Colloidal nucleic acid carrier systems based on cationic lipids are a promising pharmaceutical tool in the implementation of gene therapeutic strategies. This study demonstrates the complex behavior of DNA at the lipid− solvent interface facilitating structural changes of the lyotropic liquid-crystalline phases. For this study, the structural properties of six malonic acid based cationic lipids were determined using small-and wide-angle X-ray scattering (SAXS and WAXS) as well as differential scanning calorimetry (DSC). Selected lipids (lipid 3 and lipid 6) with high nucleic acid transfer activity have been investigated in detail because of the strong influence of the zwitterionic helper lipid 1,2-di(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine (DOPE) on the structural properties as well as of the complex formation of lipid−DNA complexes (lipoplexes). In the case of lipid 3, DNA stabilizes a metastable cubic mesophase with Im3m symmetry and an Im3m Q α c lipoplex is formed, which is rarely described for DNA lipoplexes in literature. In the case of lipid 6, a cubic mesophase with Im3m symmetry turns into a fluid lamellar phase while mixing with DOPE and complexing DNA. 50 concerning over 30 cationic phospholipids. 1 The authors were 51 able to show that not only the simple adaption of the H II c 52 structure results in an efficient gene transfection 13,19 but also 53 the pathway into the cell and structural changes on this path 54 seem to be important. For example, lamellar lipoplexes work 55 very well if upon contact with (model) cell membranes a 56 lamellar to nonlamellar phase transition occurs. 1 In summary, 57 structural properties of lipids and lipoplexes cannot be related 58 to transfection rates in a straightforward manner for all cases. 59 Moreover, it is important to understand and explain each single 60 case in order to identify different promising structures and 61 mechanisms. 62 This work focuses on the physical−chemical characterization 63 f1 of six lipids designed for gene transfection (Figure 1). 64 Synthesis and transfection results are already described. 10 65 Lipids 1−3 and 4−6 possess different headgroups. The lipid 66 chains are either saturated or unsaturated. Lipids 1 and 2 are 67 not able to incorporate colipids and show no transfection 68 activity. 10 Lipids 3 and 6 are the most promising gene transfer 69 vehicles in complexes with noncharged colipids and DNA. The 70 mixtures of lipid 6 with DOPE 2:1 (n/n) and lipid 3 with 71 DOPE 1:2 (n/n) exhibit transfection efficiencies higher than
Loading Preview
Sorry, preview is currently unavailable. You can download the paper by clicking the button above.