Nonviral gene delivery: gemini bispyridinium surfactant-based DNA nanoparticles.

The interaction with a model membrane, the formation of DNA nanoparticles, and the transfection ability of a homologous series of bispyridinium dihexadecyl cationic gemini surfactants, differing in the length of the alkyl spacer bridging the two pyridinium polar heads in the 1 and 1′ positions (P16-n with n = 3, 4, 8, 12), have been studied by means of differential scanning calorimetry (DSC), atomic force microscopy, electrophoresis mobility shift assay, and transient transfection assay measurements. The results presented here show that their performance in gene delivery is strictly related to their structure in solution. For the first time the different transfection activities of the compounds can be explained by referring to their thermodynamic properties in solution, previously studied. The compound with a spacer formed by four carbon atoms, showing unexpected enthalpic properties vs concentration in solution, is the only one giving rise to a transfection activity comparable to that of the commercial r...