Intercalation of Single-Strand Oligonucleotides between Nucleolipid Anionic Membranes: A Neutron Diffraction Study

Abstract

This contribution presents a neutron diffraction investigation of anionic lamellar phases composed of mixtures of 1-palmitoyl, 2-oleoyl phosphatidyl-nucleosides (POPN, where N is either adenosine or uridine), and POPC (1-palmitoyl,2-oleoyl-phosphatidyl-choline). Their behavior is studied for two different mole ratios and in the presence of nucleic acids. The samples are formed by the evaporation of liposomal dispersions prepared in water or in solutions containing single-strand oligonucleotides. Previous small angle X-ray scattering (SAXS) experiments on the system POPA/polyU (polyuridylic acid, high degree of polymerization, synthetic ribonucleic acid) proved that the insertion and ordering of the biopolymer in the phospholipid lamellae were driven by molecular recognition. In the present study, we extend the previous investigation to single-strand monodisperse oligonucleotides (50-mers). Structural details of the membranes were obtained from the analysis of the neutron diffraction scattering length density profiles. The evidence of direct and specific interactions, driven by molecular recognition between the nucleic polar heads of the nucleolipid and the single-strand nucleic acid, is strengthened by the comparison with identically charged bilayers formed by POPG/POPC. These results contribute to the understanding of the parameters governing the interactions between nucleolipid membranes and oligonucleotides, providing a novel strategy for the design of lipid-based vehicles for nucleic acids.

Nucleolipid nanovectors as molecular carriers for potential applications in drug delivery

“…In this frame, Berti et al reported a promising strategy for the base-specific recognition between micelles composed of dioctanoylphosphatidyluridine, a negatively charged amphiphile, and short oligoadenylic acids. [13][14][15][16] Extensive and detailed highlights on this field have been recently presented by Gissot et al 17 In this review several examples of nucleoside-or nucleotide-and oligonucleotidebased amphiphiles along with their peculiar properties are presented, which in principle may result into efficient pro-drugs. Insertion of functional reporter groups into amphiphilic nucleolipids in principle further expands the potential of this therapeutic strategy, allowing specific recognition/interaction with drugs.…”

Orientation and Specific Interactions of Nucleotides and Nucleolipids Inside Monoolein-Based Liquid Crystals

“…27,28 These assemblies provide negatively charged interfaces decorated with nucleic motifs that can complex complementary nucleic acid strands using, as the driving force, molecular recognition rather than electrostatic interactions. The recent evidence of the binding of polynucleotides to small globular micelles formed by 1,2-dioctanoylphosphatidyladenosine 29 and of the sandwiching and ordering of polynucleotides between lamellar phases of 1-oleoyl-2palmitoylphosphatidyladenosine 30,31 suggests that these nucleoamphiphiles can be exploited as compartmentalization and delivery systems for polynucleotides and oligonucleotides with relevance for many biomedical applications.…”

Nucleoside-Lipid-Based Nanoparticles for Phenazine Delivery: A New Therapeutic Strategy to Disrupt Hsp27-eIF4E Interaction in Castration Resistant Prostate Cancer

“…To overcome potential side effects, various nanovehicles such as polymeric micelles and vesicles [ 23 ], liposomes [ 24 ], and nanogels [ 25 ] have been developed. In parallel, bioinspired hybrid amphiphiles featuring both nucleosides as a lipid headgroup and lipophilic alkyl chains have recently emerged as promising molecules due to self-assembling nucleic acid-nucleolipid supramolecular systems [ 26 ] for improving drug [ 27 ] or nucleic acid delivery [ 28 ]. The molecular structure of the nucleolipids, including the base [ 29 ], the stereochemistry [ 30 ], and the charges [ 31 ], influences their drug delivery properties.…”