DNA Nanoparticles formed by Partially Fluorinated and by Hydrogenated Gemini Bispyridinium Surfactants for Nonviral Gene-Delivery

Fluorinated cationic lipids have been proposed to obtain efficient gene expression in those biological fluids containing surfactants as pulmonary surfactants or bile salts, when genes have to be delivered to the respiratory or to the biliar epithelium. This is an essential requirement in the treatment of cystic fibrosis and cystic fibrosis-associated diseases. In fact, perfluorinated compounds show peculiar properties, between which the most interesting for biomedical applications is the chemical and biological inertness, due to their high hydrophobic and lipophobic character. These originate mainly from the structure of the fluorine atoms having a larger van der Waals radius and a lower polarizability than the hydrogen atoms. This is the reason why we have studied the formation and the transfection ability of DNA nanoparticles, formed by a homologous series of highly fluorinated 1,1’-di(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl) cationic gemini surfactants, differing for the length of the alkyl spacer bridging the two pyridinium polar heads in 1,1’ position (PH2F8-n with n =3, 4, 8, 12) in comparison with the behaviour of bispyridinium diexadecyl cationic gemini surfactants, also differing for the spacer length (P16-n with n =3, 4, 8, 12). Thermodynamic techniques, atomic force microscopy (AFM), electrophoresis mobility shift assay (EMSA) and transient transfection assays measurements were employed. Their performance in gene delivery is strictly related to their structure in solution as for their hydrogenated analogues. This finding confirms that the behaviour in solution is due to a conformation change of the molecule determined by stacking interactions between the pyridinium rings, appearing at an optimum spacer length.