Gemini Surfactants Based on Bis-Imidazolium Alkoxy Derivatives as Effective Agents for Delivery of Nucleic Acids: A Structural and Spectroscopic Study

• Published in: PloS one 2015-12, Vol.10 (12), p.e0144373
• Main Authors: Pietralik, Zuzanna, Kołodziejska, Żaneta, Weiss, Marek, Kozak, Maciej
• Format: Article
• Language: English
• Subjects: Acids; Atomic force microscopy; Atomic structure; Biological membranes; Calcitriol - analogs & derivatives; Calcitriol - chemistry; Care and treatment; Cations; Chains; Circular Dichroism; Cytotoxicity; Deoxyribonucleic acid; Diagnosis; Dichroism; DNA; DNA - administration & dosage; DNA - chemistry; Dosage and administration; Dose-Response Relationship, Drug; Electric charge; Electrophoresis; Gene therapy; Gene Transfer Techniques; Genetic engineering; HeLa Cells - drug effects; Humans; Hydrophobic and Hydrophilic Interactions; Hydrophobicity; Imidazoles - chemistry; Lipids; Low concentrations; Membranes; Mickiewicz, Adam Bernard (1798-1855); Microscopy; Microscopy, Atomic Force; Nucleic acids; Parkinson disease; Physicochemical properties; Physics; Pollutants; Quaternary; Risk factors; Salts; siRNA; Spectroscopy; Surface active agents; Surface-Active Agents - administration & dosage; Surface-Active Agents - chemistry; Surface-Active Agents - toxicity; Surfactants; Toxicity; Transfection; Vectors (Biology)
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0144373

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).