Lactose-based surfactants complexable with oligonucleic acids as gene delivery agents

Abstract

AbstractAdvances in molecular medicine related to the treatment of genetic disorders and cancer require finding new pathways for gene transfer. Nonviral delivery methods rely on the application of polymers, liposomes and cationic lipid systems used as vehicle. Among these systems, there is increasing interest in surfactants, which, due to their ability to complex with nucleic acids can deliver into cell DNA or RNA molecules of almost any size, which is unattainable with viral gene delivery systems.The main aim of this study was to determine the effect of the concentration of lactose-based surfactants (zwitterionic derivatives of sulfobetaine with carbohydrate moieties) on the structure of DNA/RNA as well as to explore their abilities of nucleic acid complexation. Structural studies of DNA or RNA in complexes with surfactants of two types at various concentrations were conducted using circular dichroism (CD) spectroscopy, gel electrophoresis (GE) and synchrotron radiation small angle X-ray scattering (SR-SAXS). Our studies showed that the examined surfactants have excellent properties of forming complexes with DNA and RNA. Additionally, to determine the cytotoxicity and transfection abilities of the studied lipoplexes, preliminary tests were performed in HeLa and fibroblast cells. The obtained results suggest that these systems have relatively low toxicity; however, further research is needed in this area.