Exploring the cytotoxicity of polycations

Abstract

In the delivery of genetic material in vitro, such as mRNA-vaccines, non-viral vectors are used as the transporting system. To enable the full potential of the vectors, a positive charge on the surface is necessary, which has been proven to have cytotoxic effects. The aim is to, with polyethylene glycol with a tosylate group (mPEG-tosylate), coat the positive charge and simultaneously keep the necessary charge for the desired application. In this thesis, the cytotoxic effect of a synthesized polycation and polycations coated with mPEG-tosylate are investigated. A three step synthesis was made and tested with multiple methods to confirm the occurrence of each step and the last step was tested for its cytotoxic effect. To coat a hyperbranched polyester mPEG-tosylate was used, this was also tested with several analysis methods, and the cytotoxic effects were evaluated. The results confirm that all 3 steps of the synthesis did occur and the cytotoxic effect of the polycation was visible. It also confirms that the coating with PEG was successful and the cytotoxic effect decreased. These results suggest that further studies can be necessary, in case of what the degree of PEGylation versus the necessary charge of the polycation ratio is.