Cyclic Sulfonium Modification of Low Molecular Weight Polyethylenimine for Gene Delivery

Modification of low molecular weight polyethylenimine (PEI) is an effective method to obtain high transfection and low toxicity gene vectors. Sulfonium contains a positive charge making it a potential headgroup to interact with the negative phosphate portion of DNA. PEI 1.8k was modified with cyclic sulfonium moieties to form sulfonium PEI (SP), a series of mixed headgroup polycations which was then evaluated for DNA capability, cell tolerance and transfection abilities. The results showed that certain SPs presented stronger DNA capability that condensed DNA at a weight ratio of 4:1, and the formed particle size was in a range of 117–190 nm. The IC50 of the SPs was between 0.93–3.28 µg/mL. SP/DNA particles exhibited better cellular uptakes and transfection effects than PEI 1.8k. Through the experiment, sulfonium conjugation maintains the total positive charges of the polymer and the extra length of sulfonium increases the hydrophobic interaction of DNA. With further refinement, sulfonium can be a potential fragment to be used in non-viral gene vector discovery. Sulfonium contains a positive charge making it a potential headgroup to interact with negative phosphate portion of DNA. We constructed a group of cyclic sulfonium moieties in two steps reaction and grafted them onto PEI 1.8k to form sulfonium PEIs (SP), a series of mixed headgroup polycations. Studies showed that sulfonium modification improves gene trasfection of low molecule weight PEI.