Detalle Publicación

ARTÍCULO
A biophysical study of gene nanocarriers formed by anionic/zwitterionic mixed lipids and pillar[5]arene polycationic macrocycles
Autores: Barrán Berdón, A. L.; Martínez Negro, M.; García Río, L.; Domènech, O.; Tros de Ilarduya Apaolaza, María de la Concepción; Aicart, E.; Junquera, E. (Autor de correspondencia)
Título de la revista: JOURNAL OF MATERIALS CHEMISTRY B
ISSN: 2050-750X
Volumen: 5
Número: 17
Páginas: 3122 - 3131
Fecha de publicación: 2017
Resumen:
The use of divalent cations as mediators between anionic lipids (ALs) and nucleic acids has been explored for several years in gene therapy. However, a promising anionic lipid system which could surpass the outcomes of current cationic lipids (CLs) has not been found yet. One plausible reason for such poor efficiencies may be the impossibility of AL-DNA lipoplexes mediated by divalent cations to reach charge inversion, in contrast with the usual behavior of CL-DNA lipoplexes. In the present study, divalent bridgecations have been replaced by a multivalent positively charged macrocycle in order to see whether charge reversal is reached and how this fact may improve transfection efficiency (TE). For that purpose, an extensive biophysical and biochemical study has been carried out on lipoplexes constituted by a mixture of: (i) an anionic lipid DOPG (sodium salt of 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol)); (ii) a zwitterionic lipid DOPE (1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine), which acts as a neutral helper lipid at physiological pH 7.4; (iii) a plasmid DNA (pDNA); and (iv) a polycationic macrocycle, pillar[ 5] arene (P10+), with the role of bridging the electrostatic interaction between the anionic mixed lipids and the pDNA, also negatively charged. The studies have been done at several DOPG molar compositions (a) and pillar[ 5] arene concentrations. Electrochemical experiments (zeta potential and gel electrophoresis) have revealed that, interestingly, D