The use of amino acids for the synthesis of novel surfactants with vesicle-forming properties potentially enhances the biocompatibility levels needed for a viable alternative to conventional lipid vesicles. In this work, the formation and characterization of catanionic vesicles by newly synthesized lysine-and serine-derived surfactants have been investigated by means of phase behavior mapping and PFG-NMR diffusometry and cryo-TEM methods. The lysinederived surfactants are double-chained anionic molecules bearing a pseudogemini configuration, whereas the serinederived amphiphile is cationic and single-chained. Vesicles form in the cationic-rich side for narrow mixing ratios of the two amphiphiles. Two pairs of systems were studied: one symmetric with equal chain lengths, 2C 12 /C 12 , and the other highly asymmetric with 2C 8 /C 16 chains, where the serine-based surfactant has the longest chain. Different mechanisms of the vesicle-to-micelle transition were found, depending on symmetry: the 2C 12 /C 12 system entails limited micellar growth and intermediate phase separation, whereas the 2C 8 /C 16 system shows a continuous transition involving large wormlike micelles. The results are interpreted on the basis of currently available models for the micelle-vesicle transitions and the stabilization of catanionic vesicles (energy of curvature vs mixing entropy).

Gene delivery targeting mitochondria has the potential to transform the therapeutic landscape of mitochondrial genetic diseases. Taking advantage of the nonuniversal genetic code used by mitochondria, a plasmid DNA construct able to be specifically expressed in these organelles was designed by including a codon, which codes for an amino acid only if read by the mitochondrial ribosomes. In the present work, gemini surfactants were shown to successfully deliver plasmid DNA to mitochondria. Gemini surfactant-based DNA complexes were taken up by cells through a variety of routes, including endocytic pathways, and showed propensity for inducing membrane destabilization under acidic conditions, thus facilitating cytoplasmic release of DNA. Furthermore, the complexes interacted extensively with lipid membrane models mimicking the composition of the mitochondrial membrane, which predicts a favored interaction of the complexes with mitochondria in the intracellular environment. This work unravels new possibilities for gene therapy toward mitochondrial diseases.

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