GFP chromophore derived amphiphiles containing [12]aneN3 and biotin moieties as bio-imaging and targeting nonviral gene vectors

Abstract

Gene therapy is a promising treatment, that brings the necessary opportunity to cure human genetic and major diseases, but it is hampered by the lack of safe and efficient gene delivery vectors. In this study, four amphiphiles were derived from GFP chromophore benzylimidazolidinone (G) through modifications with oxypropyl (1) or methylene (2) linked di(triazole-[12]aneN3) (M) in the presence or absence of tumor-targeting biotin (B) moiety, GMB-1/2 and GM-1/2. The four compounds showed excellent aggregation-induced emission (AIE) characteristics, strong DNA condensation abilities, and good biocompatibility. Among them, GMB-1, which containing targeting biotin moiety and a flexible propoxy linker, showed the highest transfection efficiency in three cell lines. The luciferase transfection efficiency of GMB-1 was as high as 15.2 times that of Lipofectamine 2000 (Lipo2000) without auxiliary lipid DOPE, and its gene therapy effect of delivering the p53 gene was also significantly better than that of Lipo2000 in HeLa cells due to its obvious targeting property. Fluorescence tracing experiments indicated that GMB-1 was able to quickly carry DNA into cells, to successfully escape from lysosomes, then to release DNA, and at last to smoothly deliver DNA into the nucleus. Moreover, its EGFP transfection efficiency in zebrafish reached 1.7 times that of Lipo2000. The excellent performance of GMB-1 demonstrated that the appreciative incorporation of GFP chromophore, di(triazole-[12]aneN3), and biotin moieties into the nonviral gene vectors provided a promising strategy for their clinical applications.