Gene therapy has
the therapeutic potential to address a multitude
of health problems, and it also has utility in different domains of
science. However, its applications are plagued due to the absence
of a suitable, safe, efficient, selective, and universal vector, which
could help in delivering the desired nucleic acid cargo to the site
of action. Though viral vectors are efficient, they pose various health
risks. Different types of synthetic agents have been tried as nucleic
acid vectors by researchers but with limited success. Gemini amphiphiles
(GAs) are a class of synthetic surfactants having biscationic heads
with attached hydrophilic and lipophilic groups. Herein, we synthesized
two classes of GAs differing in the chemical nature and length of
the linkers, head groups, and lipophilic chains. The resulting compounds
were evaluated for their efficiency to transfect A549 and HeLa cell
lines with a β-galactosidase reporter plasmid. A 3-oxypentyl
linker, a monohydroxyethyl head group, and a tetradecyl moiety as
the lipophilic chain offered the best transfection efficiency (compound
10BIII
). Dioleoylphosphatidylethanolamine (DOPE) as the helper
lipid improved the transfection efficacy of the GAs in the absence
of serum. In the presence of serum, DOPE and cholesterol, as the helper
lipids, improved the transfection efficacy of the resulting formulations.
The synthesized GAs showed concentration-dependent toxicity in the
MTT assay. Biodistribution studies using 99
m
Tc-labeled
lipoplexes indicated that the lipoplexes got concentrated in some
vital organs such as the spleen, liver, and lungs.