Interactions of Cationic Lipids with DNA: A Structural Approach

Langmuir : the ACS Journal of Surfaces and Colloids
Matthias DittrichChristian Wölk

Abstract

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 Qαc 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.

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Citations

Dec 31, 2019·Colloids and Surfaces. B, Biointerfaces·Julia Janina SchüerShashank Reddy Pinnapireddy
Dec 29, 2020·Chemistry and Physics of Lipids·Federica PontiGabriele Candiani
Jul 20, 2021·Chemistry and Physics of Lipids·Nina Královič-KanjakováDaniela Uhríková
Mar 7, 2019·Langmuir : the ACS Journal of Surfaces and Colloids·Stephanie TasslerGerald Brezesinski

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