title: The effect of fluorination on the transfection efficacy of surface-engineered dendrimers.
abstract: Dendrimers have shown great promise in the design of high efficient and low cytotoxic gene vectors. In this study, we synthesized a list of fluorobenzoic acid-modified dendrimers by a facile synthetic route and explored their potential applications as non-viral gene vectors. Fluorination on the aromatic rings significantly improves the transfection efficacy of benzoic acid-modified dendrimers. The transfection efficacy increases with increasing number of fluorine atoms on the aromatic rings of the conjugated benzoic acid. The most efficient conjugate shows superior efficacy to polymer-based commercial reagents such as SuperFect and PolyFect, and comparable efficacy to lipid-based commercial reagents such as Lipofectamine 2000. In addition, the fluorobenzoic acid-modified dendrimers show low cytotoxicity on the transfected cells. The improved transfection efficacy of fluorobenzoic acid-modified dendrimers is due to enhanced cellular uptake and/or easier DNA unpacking behavior compared to non-modified dendrimers. These results provide a new fluorination strategy to generate a library of highly efficient and non-cytotoxic polymeric gene vectors.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, PR China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, PR China. Electronic address: yycheng@mail.ustc.edu.cn.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D001565:Benzoates / Q000737:chemistry; D016923:Cell Death; D004247:DNA / Q000378:metabolism; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry*; D004587:Electrophoresis, Agar Gel; D004705:Endocytosis; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D054879:Halogenation; D006367:HeLa Cells; D006801:Humans; D057446:Hydrodynamics; D008156:Luciferases / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D055672:Static Electricity; D013499:Surface Properties; D014162:Transfection / Q000379:methods*
chemical_list: D001565:Benzoates; D050091:Dendrimers; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D004247:DNA; D008156:Luciferases
keywords: Cytotoxicity; Dendrimer; Fluorous effect; Gene delivery; Transfection efficacy