A novel gene delivery approach to face cystic fibrosis by non-viral vectors based on niocarbosomes

Non-viral vectors are a promising approach to address genetic-based diseases, such as cystic fibrosis (CF), due to their safety profile and lower production costs compared to viral vectors. This study includes the development of conventional niosomes using the oil-in-water (o/w) emulsion technique, which were based on 2,3-di(tetradecyloxy)propan-1-amine (DTPA) cationic lipid and polysorbate 85 as a non-ionic surfactant. Additionally, novel niosomes referred to as niocarbosomes were developed incorporating carboxyl-functionalised single-walled carbon nanotubes (SWNT-COOH) as a helper component. The physicochemical properties of formulations and their complexes obtained upon the addition of genetic material, referred to as nioplexes and niocarboplexes respectively, were thoroughly examined using transmission electron microscopy (TEM), dynamic light scattering (DLS), and small-angle X-ray scattering (SAXS) techniques. Furthermore, the formation of protein corona around the non-viral vectors was investigated upon exposure to human blood plasma. Niocarbosomes complexed with pEGFP reporter gene transfected around 26% of treated cells mainly via the lipid rafts pathway, with a cell viability rate of 85%. Next, these niocarbosomes were complexed with a therapeutic plasmid coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein (pGM169) for CF treatment. Treated cells showed a 65% increase in CFTR functionality compared to untreated cells, demonstrating the potential of niocarbosome non-viral gene delivery systems to face CF disease.