LAUSR

Low transfection efficacy of non‐viral gene vectors restricts their applications. In this paper, N1,N3‐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.