Sulfonium Lipids: Synthesis and Evaluation as DNA Delivery Vectors.

Background: Cationic lipids can be used as nonviral vectors in gene delivery therapy. Most cationic lipids contain quaternary ammonium that can bind to negative phosphates of the plasmid. In this study, sulfonium-a trialkylated sulfur cation was adopted in the synthesis of a series of cationic lipids which were evaluated for their ability to function as gene delivery vectors.

Methods: The sulfonium lipids were synthesized by condensing cyclic thioether and aliphatic carbon chains with ethoxy linkage and the structure was characterized by NMR and mass. The DNA condensing abilities of sulfonium lipids were evaluated using a gel retardation experiment. Sulfonium lipids/ DNA condensates were measured for particle size and Zeta potential. The cytotoxicity of sulfoniums was evaluated with the MTT assay. The intracellular uptake of sulfonium lipid/DNA complexes was observed with a fluorescence microscope.

Results: The results showed that the sulfonium head can effectively bind to the phosphate of DNA. When the S/P ratio is larger than 10/1, sulfonium lipids with longer carbon chains can completely condense DNA to form a nanoparticle with particle size ranging from 135 nm to 155 nm and zeta potential ranging from 28 mV to 42 mV. The IC50 of sulfonium lipids on HepG2 cells ranged from 2.37 μg/mL to 3.67 μg/mL. Cellular uptake experiments showed that sulfonium lipids/DNA condensate can be taken into cells.

Conclusion: Sulfonium lipids can effectively condense DNA and transfer DNA into cells. The sulfonium compound is worth further development to reduce the cytotoxicity and increase the transfection rate as gene vectors.