Lysine derivated cationic lipid like genetic carriers: C6(NaLK)2

AL. BARRAN-BERDON ; MÓNICA MUÑOZ-UBEDA; MARÍA BELÉN SIERRA; CLARA AICART-RAMOS; LOURDES PEREZ; MARIA ROSA INFANTE; EMILIO AICART; ELENA JUNQUERA

Porto

Congreso; 4th Iberian Meeting on Colloids and Interfaces; 2011

Lysine derivated cationic lipid like genetic carriers: C6(NaLK)2 Ana Lilia. Barran-Berdoni*, Monica Muñoz-Ubedal, Maria Belen Sierral, Clara Aicart Ramos2, Lourdes Perez3, Maria Rosa Infante3, Emilio Aicartl and Elena Junquera I Grupo Química Coloidal y Supramolecular, Dpto. Química Física I, Fac. Ciencias Químicas, Universidad Complutense de Madrid, 28040-Madrid, Spain 2 Departamento de Bioquímica y Biología Molecular I, Fac. Ciencias Químicas, Universidad Complutense de Madrid, 28040-Madrid, Spain. 3Departamento de Tecnología de Tensioactius, Instituto de Investigaciones Químicas y Ambientales, CS/C, Barcelona, Spain *anbarran@pdi.ucm.es Gene carriers based on lipids constitute a promising technique to deliver DNA into cells for gene therapy. However, their efficiency must be associated with their biocompatibility, a feature that may be greatly improved by using lysine-derived lipids. Lipoplexes constituted by plasmidic DNA pEGFP-C3 and mixed cationic liposomes consisting of several percentage of the cationic lysine- derived lipid C6(NaLK)2 and the zwitterionic lipid, 1,2-dioleoyl-sn-glycero-3-phosphoetanolamine (DOPE) have been analyzed by means of electrophoretic mobility/zeta potential, small angle X-ray scattering (SAXS), and gel red fluorescence intercalation assays. Experimental studies have been carried out at several liposome and lipoplex compositions, defined in terms of cationic lipid molar fraction, a, and either the mass or charge ratios of the lipoplex, respectively. The electrophoretic mobility/zeta potential results indicate that C6(NaLK)2 /DOPE liposomes compact and condense the plasmidic DNA at their cationic surfaces by means of a strong electrostatic interaction. Furthermore, for a given DNA concentration, the positive charges of cationic Liposomes compensate the effective negative charges of DNA phosphate groups at the isoneutrality L/D ratio, (L/D)f which decreases with the cationic lipid content of the mixed liposome. In addition, this effective charge of the DNA in the lipoplex has been determined from the experimental (L/D)f, at the whole studied lipid molar fractions, a,. SAXS diffractograms at several lipid molar fractions, a, show that, irrespectively of the lipoplex charge ratio, C6(NaLK)2 /DOPE-DNA lipoplexes depict a lamellar structure, La, when the cationic lipid content in the mixed Liposomes is a> 0.2, while for a lower cationic lipid content (a = 0.2), the lipoplexes show an inverted hexagonal structure, HII, usually related with an improved cell transfection efficiency. Acknowledgements: We thank the European Synchrotron Radiation Facility (ESRF) Bearnline 16, Grenoble (France) for SAXS experiments [1] A. Rodriguez-Pulido, F. Ortega, E. Aicart, 0. Llorca and E. Junquera, J. Phys. Chem. 2008, B 112,12555-12565, [2] M. Murioz-ljbeda, A. Rodriguez-Pulido, A. Nogales, A. Martin-Molina, E. Aicart and E. Junquera, Biomacromolecules 2010, 11, 3332-3340. [3] M. Mulioz-Obeda, A. RodrIguez-Pulido, A. Nogales, 0. Llorca, M. Quesada-Perez, A. Martin- Molina, E. Aicart and E. Junquera, Soft Matter 2011, (DOI:10.1039/elsm05352c). [4] M. R. Infante, L. Perez, M. C. Moran, R. Pons, M. Mitjans, M. P. Vinardell, M. T. Garcia and A. Pinazo, Eur. J. Lipid Sci. Technol. 2010, 112, 110-121.