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      Polymers modified with double-tailed fluorous compounds for efficient DNA and siRNA delivery.

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          Abstract

          Cationic polymers are widely used as gene carriers, however, these polymers are usually associated with low transfection efficacy and non-negligible toxicity. Fluorination on polymers significantly improves their performances in gene delivery, but a high density of fluorous chains must be conjugated on a single polymer. Here we present a new strategy to construct fluorinated polymers with minimal fluorous chains for efficient DNA and siRNA delivery. A double-tailed fluorous compound 2-chloro-4,6-bis[(perfluorohexyl)propyloxy]-1,3,5-triazine (CBT) was conjugated on dendrimers of different generations and low molecular weight polyethylenimine via a facile synthesis. The yielding products with average numbers of 1-2 conjugated CBT moieties showed much improved EGFP and luciferase transfection efficacy compared to unmodified polymers. In addition, these polymers show high siRNA delivery efficacy on different cell lines. Among the synthesized polymers, generation 1 (G1) dendrimer modified with an average number of 1.9 CBT moieties (G1-CBT1.9) shows the highest efficacy when delivering both DNA and siRNA and its efficacy approaches that of Lipofectamine 2000. G1-CBT1.9 also shows efficient gene silencing in vivo. All of the CBT-modified polymers exhibit minimal toxicity on the cells at their optimal transfection conditions. This study provides a new strategy to design efficient fluorous polymers for DNA and siRNA delivery.

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          Author and article information

          Journal
          Acta Biomater
          Acta biomaterialia
          Elsevier BV
          1878-7568
          1742-7061
          Aug 2015
          : 22
          Affiliations
          [1 ] Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, PR China.
          [2 ] 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.
          Article
          S1742-7061(15)00208-1
          10.1016/j.actbio.2015.04.037
          25937003
          35512835-1075-4d07-b03b-80f5ddf4b5cf
          History

          Dendrimer,Fluorination,Gene transfection,Polymer,siRNA
          Dendrimer, Fluorination, Gene transfection, Polymer, siRNA

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