Cationic polymers with different backbones were characterized regarding their performance at different steps of the gene delivery process. The interaction with plasmid DNA (pDNA), cytotoxicity, uptake of pDNA, endosomal escape and protein expression in different cell lines were investigated using methods like fluorometric assays, dynamic light scattering, flow cytometry and confocal laser scanning microscopy. Starting with homopolymers of different degrees of polymerization and different cationic moieties, a positive correlation between toxicity and endosomal escape was demonstrated. By combination with hydrophobic functionalities either within block copolymers resulting in cationic micelles or within statistic copolymers, the transfection efficiency was increased even in hard-to-transfect leukemia cells. To reduce the accompanying toxicity, further hydrophilic neutral and/or anionic functionalities were introduced either within block copolymers or as an additional layer outside the preformed cationic micelles. Different factors influenced the efficiency-toxicity ratio of the polymers, such as the ratio, type and combination method of cationic and anionic/hydrophilic moieties. The introduction of only anionic moieties was most promising and led to an increase in viability while maintaining high transfection efficiencies comparable to the cationic micelle. The combination of cationic micelle and anionic-hydrophilic block copolymer exhibited the highest shielding efficiency with decreased but still moderate transfection efficiency, rendering it suitable for long circulation times and targeted delivery. This thesis illustrates the high suitability of cationic polymers for gene delivery and their optimization in different parameters towards high cell viability while maintaining superior gene delivery efficiency. Hence, polymers represent promising tools for future gene therapy and further (in vivo) studies are required to transfer these results to humans
