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BACKGROUND Cationic lipids can be used as nonviral vectors in gene delivery therapy. Most cationic lipids contain quaternary ammonium that can bond 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 ability as gene delivery vectors. METHODS The sulfonium lipids were synthesized by condensing cyclic thioether and aliphatic carbon chains with ethoxy linkage and characterized the structure 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 MTT assay. The intracellular uptakes of sulfonium lipid/DNA complexes were observed with a fluorescence microscope. RESULTS The results showed that the sulfonium head can effectively bond to the phosphate of DNA. When 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 of further development to reduce the cytotoxicity and increase transfection rate as gene vectors.