Self-assembling complexes between binary mixtures of lipids with different linkers and nucleic acids promote universal mRNA, DNA and siRNA delivery.

Autor: Colombani T; CRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, France., Peuziat P; CRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, France., Dallet L; CBMN UMR-CNRS 5248, Université de Bordeaux IPB, Pessac, France., Haudebourg T; CRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, France., Mével M; CRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, France., Berchel M; UMR CNRS 6521, IFR 148 ScInBioS, Université de Bretagne Occidentale, Université Européenne de Bretagne, Brest, France., Lambert O; CBMN UMR-CNRS 5248, Université de Bordeaux IPB, Pessac, France., Habrant D; In-Cell-Art, Nantes, France., Pitard B; CRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, France; In-Cell-Art, Nantes, France. Electronic address: bruno.pitard@univ-nantes.fr.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2017 Mar 10; Vol. 249, pp. 131-142. Date of Electronic Publication: 2017 Feb 01.
DOI: 10.1016/j.jconrel.2017.01.041
Abstrakt: Protein expression and RNA interference require efficient delivery of DNA or mRNA and small double stranded RNA into cells, respectively. Although cationic lipids are the most commonly used synthetic delivery vectors, a clear need still exists for a better delivery of various types of nucleic acids molecules to improve their biological activity. To optimize the transfection efficiency, a molecular approach consisting in modifying the chemical structure of a given cationic lipid is usually performed, but an alternative strategy could rely on modulating the supramolecular assembly of lipidic lamellar phases sandwiching the nucleic acids molecules. To validate this new concept, we synthesized on one hand two paromomycin-based cationic lipids, with either an amide or a phosphoramide linker, and on the other hand two imidazole-based neutral lipids, having as well either an amide or a phosphoramide function as linker. Combinations of cationic and helper lipids containing the same amide or phosphoramide linkers led to the formation of homogeneous lamellar phases, while hybrid lamellar phases were obtained when the linkers on the cationic and helper lipids were different. Cryo-transmission electron microscopy and fluorescence experiments showed that liposomes/nucleic acids complexes resulting from the association of nucleic acids with hybrid lamellar phases led to complexes that were more stable in the extracellular compartment compared to those obtained with homogeneous systems. In addition, we observed that the most active supramolecular assemblies for the delivery of DNA, mRNA and siRNA were obtained when the cationic and helper lipids possess linkers of different natures. The results clearly show that this supramolecular strategy modulating the property of the lipidic lamellar phase constitutes a new approach for increasing the delivery of various types of nucleic acid molecules.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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