Synthesis of folic acid-containing imidazolium copolymers for potential gene delivery applications

Folic acid conjugation onto poly(1-vinylimidazole) generates imidazolium copolymers for potential receptor-mediated nonviral gene delivery. Homopolymer quaternization with various tBoc-protected bromoalkylamines imparts a permanent charge for DNA complexation. Incorporation of primary amine groups provides a site for folic acid conjugation onto imidazolium copolymers. DNA binding, cytotoxicity, and in vitro transfection in HeLa cells reveal structure-property-transfection relationships for the imidazolium copolymers. Luciferase expression assays establish that primary amine conjugation onto imidazolium copolymers up to 30 mol% fails to improve transfection efficiency. In sharp contrast, incorporation of folic acid onto the copolymers improves transfection efficiency 250-fold. Synthesis of amine-containing imidazolium copolymers with folic acid generates macromolecules for nonviral gene delivery. Low incorporation of folic acid onto the copolymers remains ideal for nonviral gene delivery as large concentrations produce water-insoluble copolymers. The incorporation of folic acid offers a safe and effective avenue to tailor imidazolium copolymer gene delivery.