DNA Condensation into Inverted Hexagonal Phase in Aqueous Dispersion of Poly(Ethylene)-Functionalized Dioleoylphosphatidylethanolamine and Metal Cations

Abstract

We report the x-ray diffraction study of the structure and phase behavior of mixtures of dioleoylphosphatidylethanolamine (DOPE) and poly(ethyleneglycol)-functionalized DOPE (DOPE:PEG(350)) in aqueous dispersions of DNA and bivalent metal cations. Characterization of the phase behaviour of DOPE/DOPE:PEG(350) mixtures in presence of metal cations without DNA is also performed: over a definite amount of the PEG-lipid component, a phase transition from the inverted hexagonal phase H _II to the bicontinuous inverted cubic phase, with space group Pn3m is induced. Moreover, it is shown that at low concentration of PEG-lipid component, the inverted hexagonal phase is found on adding DNA to the aqueous dispersions of DOPE/DOPE:PEG and metal cations. This structure consists of cylindrical DNA strands coated by neutral lipid monolayers and arranged on a two-dimensional hexagonal lattice. The results here shown represent the first experimental evidence of a self-assembled formation of an inverted hexagonal complex structure in aqueous dispersions of DNA, metal cations and liposomes made of mixtures of pure and pegylated lipids. The surface functionalization with the PEG-lipid and the evidence of the formation of the complexes are important results in the perspective of the development of appropriate vectors for drug delivery and gene transfection.

Keywords:

• complexes
• DOPE
• DNA
• PEG
• x-ray diffraction