Max Planck Institute of Colloids and Interfaces , Science Park Potsdam-Golm, Am Mühlenberg 1 , 14476 Potsdam , Germany.
Photon Science - DESY , Notkestrasse 85 , 22607 Hamburg , Germany.
Langmuir. 2018 Dec 11;34(49):14858-14868. doi: 10.1021/acs.langmuir.8b01635. Epub 2018 Sep 13.
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(9 Z-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 Im3 m symmetry and an Im3 m Q lipoplex is formed, which is rarely described for DNA lipoplexes in literature. In the case of lipid 6, a cubic mesophase with Im3 m symmetry turns into a fluid lamellar phase while mixing with DOPE and complexing DNA.
基于阳离子脂质的胶态核酸载体系统是实施基因治疗策略的一种很有前途的药物工具。本研究证明了 DNA 在脂质-溶剂界面处的复杂行为，促进了溶致液晶相的结构变化。在这项研究中，使用小角和广角 X 射线散射（SAXS 和 WAXS）以及差示扫描量热法（DSC）来确定六种基于丙二酸的阳离子脂质的结构特性。由于带电荷的辅助脂质 1,2-二（9Z-十八烯酰基）-sn-甘油-3-磷酸乙醇胺（DOPE）对结构特性以及脂质-DNA 复合物（脂质体）的复杂形成具有强烈影响，因此具有高核酸转移活性的选定脂质（脂质 3 和脂质 6）已被详细研究。在脂质 3 的情况下，DNA 稳定了具有 Im3 m 对称性的亚稳立方中间相，形成了 Im3 mQ 脂质体，这在文献中很少描述 DNA 脂质体。在脂质 6 的情况下，当与 DOPE 混合并与 DNA 络合时，具有 Im3 m 对称性的立方中间相转变为流体层状相。
