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 structurepropertytransfection 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.