Structure and Phase Transformation of Oligodeoxynucleotide/Lipid Lipoplexes on Solid Supports

Abstract

Lipoplexes are composed of lipids and nucleic acids and have an ordered multilamellar structure with a periodic 1D array of parallel nucleic acid strands in the lipid bilayers. We report a low-angle X-ray diffraction study on solid-supported lipoplex films composed of synthetic single-stranded oligodeoxynucleotides (ssODN) and lipids. The ssODN molecules distribute sparsely in the headgroup regions when the weight concentration of the ssODN in the lipoplex is low. The lipoplex separates into two phases, an ODN-poor phase and an ODN-rich phase, when the weight concentration of the ssODN is increased beyond a level at which the ssODN molecules contact each other so that some regions of the lipid bilayers must accommodate two layers of the ssODN. The phase separation is a result of the fusion of such regions to minimize the total interfacial energy of the system. The ssODN molecules distort the lipid bilayers in the ODN-poor phase. The local area per lipid molecule is increased by the distortions so that the interbilayer distance of the lipoplex film is smaller than that of the lipid film without the ssODN. The ODN-rich phase has a much larger interbilayer distance because two layers of ssODN are intercalated into each lipid bilayer. The ssODN molecules are tightly compacted, and the lipid bilayers are not distorted in the ODN-rich phase.

Demixing and crystallization of DODAB in DPPC–DODAB binary mixtures

“…Lipoplexes, the complexes of DNA and cationic lipids, have been widely studied because of their potential use as nonviral gene delivery systems. [1][2][3][4][5][6][7][8][9][10] Here, DNA is packed in various organized lipid structures such as lamellar and hexagonal phases. [11][12][13][14] The lamellar phase consists of smectic-like arrays of stacked lipid bilayers with DNA monolayers intercalated within the water gaps.…”

Materialistic Interfaces with Nucleic Acids: Principles and Their Impact

“…First, the hydrophobic effect could promote the assembly of nucleic acids in the presence of lipids and stabilized the hybrids. [ 73 ] Thus, the loading of nucleic acid drugs could be achieved based on the cover of lipid NPs. Additionally, the cationic liposomes which were artificially synthesized or derivatized from natural products could couple with negatively charged nucleic acids based on the mechanism of electrostatic interaction.…”