Abstract
The success rate of gene therapy depends on the efficient transfection of genetic material into cells. The golden mean between harmlessness and high effectiveness can be provided by synthetic lipid-like molecules that are similar to the components of biological membranes. Cationic gemini surfactants are one such moiety and because of their favourable physicochemical properties (double positive electric charge, reduced toxicity, low values of critical micelle concentration), they show great potential as delivery system components for genetic material in gene therapy. The aim of this study was to investigate the process of the complexation of cationic gemini surfactants with nucleic acids: double-stranded DNA of different sizes (21 bp, ~185 bp, ~20 kbp) and siRNA (21 bp). The tested series of dicationic surfactants consists of bis-imidazolium quaternary salts with varying lengths of hydrophobic side chains (m = 5, 6, 7, 8, 9, 11, 12, 14, 16). On the basis of the data obtained by circular dichroism spectroscopy and electrophoresis, we concluded that the studied gemini surfactants with long side chains effectively bind nucleic acids at low concentrations, which leads to the formation of stable lipoplexes. Images obtained by atomic force microscopy also confirmed the formation of vesicular structures, i.e., complexes between DNA and surfactants. The cytotoxicity of selected surfactants was also tested on HeLa cells. The surfactant toxicity significantly depends on surfactant geometry (the length of hydrophobic chain).
Highlights
Modern therapeutic approaches should not focus solely on treating the symptoms and mitigating the effects and extend to the molecular origins of disease
The aim of our work was to investigate the influence of the hydrophobic alkoxymethyl side chain length of gemini surfactants on the ability to effectively bind nucleic acids and form stable complexes, which could potentially be used for future therapeutic tests
A series of dicationic gemini surfactants 1,5-bis(1-imidazolilo-3-alkoxymethyl) pentane dichloride were synthesized according to a procedure reported previously [28] and were a generous gift from dr Andrzej Skrzypczak (Poznań University of Technology, Poland)
Summary
Modern therapeutic approaches should not focus solely on treating the symptoms and mitigating the effects and extend to the molecular origins of disease. Knowledge of the aetiology of a particular disease can enable the correction of organism’s dysfunction, stop the disease’s progression and (sometimes) even completely undo its effects without the side effects associated
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