Fluorinated poly(propylenimine) dendrimers as gene vectors
2014
The use of poly(propylenimine) (PPI) dendrimers as gene delivery vectors is limited by their low transfection efficacy and serious cytotoxicity. In this study, we prepare a series of efficient and low cytotoxic gene vectors based on PPI dendrimers using a facile fluorination strategy. Fluorinated G3, G4, and G5 PPI dendrimers show comparable or superior transfection efficacies to six representative transfection reagents such as Lipofectamine 2000, jetPEI, branched poly(ethyleneimine), SuperFect, PolyFect, as well as arginine-modified dendrimer on both HEK293 and HeLa cells. These fluorinated PPI dendrimers exhibit low cytotoxicity on the transfected cells because they achieve optimal transfection efficacy at extremely low nitrogen to phosphorus (N/P) ratios. In addition, the synthesized materials show high transfection efficacy on 3D multicellular spheroids. These results demonstrate that fluorination is a promising strategy to improve the transfection efficacy of PPI dendrimers while reducing the cytotoxicity of these cationic polymers.
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