Fluorinated poly(propylenimine) dendrimers as gene vectors.
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.
Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, PR China.
Hongmei
H
Liu
The Second Military Medical University, Changzheng Hospital, Department of Orthopedic Oncology, Shanghai PR China.
Yu
Y
Wang
Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, PR China.
Mingming
M
Wang
The Second Military Medical University, Changzheng Hospital, Department of Orthopedic Oncology, Shanghai PR China.
Jianru
J
Xiao
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.
Yiyun
Y
Cheng
D001388:Aziridines / Q000737:chemistry* / Q000494:pharmacology; D050091:Dendrimers / Q000737:chemistry* / Q000494:pharmacology; D005465:Fluorocarbon Polymers / Q000737:chemistry* / Q000494:pharmacology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000737:chemistry*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D014162:Transfection
D001388:Aziridines; D050091:Dendrimers; D005465:Fluorocarbon Polymers; C031132:propyleneimine
Dendrimer; Fluorination; Gene transfection; Poly(propylenimine)