Topology-Dependent Application of Fluorinated bPEI and PAMAM G4 in Gene Delivery

Abstract Existing research of single polymer systems has primarily focused on the modification and optimization, with limited systematic comparisons of the performance evolution and gene transfection differences between branched polyethyleneimine (bPEI) and dendritic polyamide-amine (PAMAM) after fluorination modification. In this study, a series of fluorinated polymers were prepared by fluorinating 25 kDa bPEI and PAMAM G4 using heptafluorobutyric anhydride. The pEGFP plasmid was employed as a model gene. The gene transfection efficiencies of both types of materials before and after fluorination were systematically compared and evaluated using fluorescence analysis, flow cytometry, and in vivo imaging techniques. The results demonstrated that fluorination significantly enhanced transfection efficiency under serum-containing conditions. PAMAM G4-F773 in particular exhibited superior performance compared to fluorinated bPEI and the commercial Lipofectamine 2000 transfection reagent. This study represents the first systematic comparison of transfection performance between these two types of fluorinated polymers, providing crucial insights for rational design of gene delivery vectors.