1110. Selective Chemical Modification on Polyethylenimine and Its Effects on Transfection Efficiency and Cytotoxicity

Abstract

Top of pageAbstract Branched polyethylenimine 25,000 is an efficient cationic polymeric transfection agent that possesses both DNA condensation and endosome lytic functionalities. Its abundant primary, secondary and tertiary amine groups contribute to transfection activity as well as significant toxicity to cells. To better understand to what extend each type of amine group is responsible for transfection and toxicity, selective chemical modification was performed on individual primary, secondary amine groups or both types on PEI by acylation (charge elimination) or reductive amination (transformation to tertiary amines). The resulted PEI derivatives have different amounts of each type of amine groups and varied degrees of charge density. Here we show the synthesis of these derivatives and the characterization in relationship to DNA binding, transfection efficiency, and cytotoxicity. Our initial results suggest that primary amine groups are mainly responsible for high affinity of DNA binding and toxicity, and that selective elimination of a portion of the primary amine groups resulted in polymers with enhanced gene transfection efficiency and significantly reduced toxicity. Secondary amine groups also contributed to a certain degree of toxicity while polymers that contain tertiary amine groups to the entirety are still transfectionally competent. These results add to the existing knowledge about the structural details of PEI25,000 relevant to its biological activities.