Amino-ethoxilated fluorinated amphiphile: Synthesis, self-assembling properties and interactions with ssDNA

• Published in: Journal of fluorine chemistry 2012-03, Vol.135, p.330-338
• Main Authors: Dupuy, Nicolas, Pasc, Andreea, Parant, Stéphane, Fontanay, Stéphane, Duval, Raphaël E., Gérardin, Christine
• Format: Article
• Language: English
• Subjects: Bacteriology; Fluorinated surfactant; Life Sciences; Medication; Microbiology and Parasitology; Pharmaceutical sciences; ssDNA-nanovectors; Vesicles; Virology
• ISSN: 0022-1139; 1873-3328
• DOI: 10.1016/j.jfluchem.2011.12.017

A monocatenar surfactant, noted F9NH(EO)2NH2 and consisting of (i) a fluorinated hydrophobic tag responsible of self-assembling, (ii) an ethylenoxide moiety sufficiently hydrophilic to avoid precipitation of the lipid-ODN complex and (iii) a protonated at physiological pH primary amine responsible of binding, was synthesized and its surface chemical properties were examined with the aim to have a highly water-soluble surfactant spontaneously forming vesicles entrapping drug or gene carriers. [Display omitted] ► Surfactant F9NH(EO)2NH2 featuring a single perfluoroalkyl chain spontaneously forms vesicles in water. ► This is the first example of single chain surfactant as vesicles carriers for ssDNA. ► Below CAC micellization occurs, up to a certain value where DNA-vesicles are formed. ► F9NH(EO)2NH2 is not toxic for human cells (MRC-5) below 40μM. Fluorinated compounds are not only more hydrophobic than their hydrogenated counterparts but also oleophobic. This makes them interesting for biomedical applications. They form a large variety of supramolecular architectures and, if appropriately designed, they spontaneously form vesicles. Herein we report the synthesis of novel monocatenar fluorinated surfactant, named F9NH(EO)2NH2, its use as ssDNA vector with potential applications in gene delivery or RNA interference. The molecular structure of the amphiphilic compound was designed in three parts: (i) a fluorinated hydrophobic tag responsible of self-assembling, (ii) a flexible and hydrophilic ethylenoxide moiety as polar head and (iii) a protonated at physiological pH primary amine responsible of binding. Surface tension, dynamic light scattering (DLS) measurements, and TEM studies showed that the monocatenar surfactant F9NH(EO)2NH2 spontaneously self-assembles into vesicles. This represents another example in addition to the few existing in the literature and it highlights the unique properties of the fluorinated tail. Interactions between ssDNA and cationic monocharged F9NH(EO)2NH2 were probed by static light scattering (SLS), fluorescence and circular dichroism (CD). F9NH(EO)2NH2 was found to exclude ethidium bromide (EB) from ssDNA/EB complex, and this process was dependent on the ssDNA concentration and on the charge ratio surfactant to ssDNA. CD spectra showed that by increasing the surfactant concentration, ssDNA undergoes a continuous conformational transition from native B-form to a more ordered phase (Z+/Z−≤3) and then to a less ordered phase (Z+/Z−≥