Dicationic DEGA-based lipid systems for gene transfer and delivery: Supramolecular structure and activity

Abstract

A novel type of dicationic lipid (DEGA) based on L-Glutamic acid, with different spacer arms between the two polar heads of lipid chain groups, was recently synthesised. The potential of cationic liposomes, prepared from DEGA, for gene delivery was tested by monitoring gene expression in human cancerous cells. Besides, Coherent Phase Microscopy was applied to study the DNA-DEGA complex formation. Encapsulation of DNA molecules by the cationic liposomes, and a significant increase in the optical density and phase height were observed for the complex, compared to individual liposomes. The incubation time was found to play an important role in the condensation and/or encapsulation of DNA molecules by the cationic lipid. Moreover, the conformational and structural peculiarities of DNA-DEGA complexes were studied using Atomic Force Microscopy (AFM). It is shown that short spacer DEGA liposomes form morphologically more compact particles with plasmid DNA of spherical and toroidal form (50-120nm) and effectively transfer functional genes in eukaryotic cellular lines; while those with long spacers form unstable amorphous aggregates and were not potent for cell transfection.