Efficient Gene Delivery Based on Guanidyl‐Nucleic Acid Molecular Interactions

Low transfection efficacy of non-viral gene vectors restricts their applications. In this paper,N-1,N-3-dicarbamimidoyl-5-methylisophthalamide (BGG) is designed as a functional group, in which two guanidyls are located at the meta positions of an aryl ring. BGG is conjugated with PAMAM G5 (G5-BGG) and G5-BGG/DNA complex is dispersed into a polyvinyl alcohol (PVA) hydrogel for local injection. Molecular docking, NMR, IR and Isothermal titration calorimetry (ITC) experiments demonstrate that G5-BGG has multiple molecular interactions with nucleic acids, which yield high binding affinity toward nucleic acids. Interestingly, the in vitro transfection efficiency and serum stability of G5-BGG are significantly improved when the BGG modification ratio is just one. The integrated G5-BGG/DNA complex is released from a PVA hydrogel sustainably, crosses the cell membrane and escapes from endosome/lysosome. After local injection only once, these features of the G5-BGG/DNA-loaded PVA hydrogel are found to improve antitumor efficiency in vivo, and antitumor efficiency is significantly better than PEI 25K. The results confirm that BGG is a potential group for developing non-viral gene vectors with high transfection efficacy.