Dendronised block copolymers as potential vectors for gene transfection.

A series of block copolymers containing a dendronised cationic block for efficient DNA binding and a poly(ethylene glycol) block for encapsulation of the complex were synthesised in a modular fashion using a combination of click chemistry and ring-opening metathesis polymerisation. DNA binding experiments, investigated using gel electrophoresis, dynamic light scattering and transmission electron microscopy, showed that all polymers prepared in this study strongly complex DNA and self-assemble into polyion complex micelles with apparent hydrodynamic radii ranging from 20-120 nm at physiological pH (7.4). The in vitro transfection efficiency and toxicity of these potential non-viral vectors were also evaluated in HeLadouble dagger cells using plasmid DNA encoding for green fluorescent protein as the reporter gene.

[1]  F. Diederich,et al.  Dendritic vectors for gene transfection , 2007 .

[2]  Jason P. Jordan,et al.  Small-molecule N-heterocyclic-carbene-containing olefin-metathesis catalysts for use in water. , 2007, Angewandte Chemie.

[3]  Jong-sang Park,et al.  Synthesis and characterization of a novel arginine-grafted dendritic block copolymer for gene delivery and study of its cellular uptake pathway leading to transfection. , 2007, Bioconjugate chemistry.

[4]  Andreas M. Nyström,et al.  Characterization of Poly(norbornene) Dendronized Polymers Prepared by Ring-Opening Metathesis Polymerization of Dendron Bearing Monomers , 2006 .

[5]  O. Danos,et al.  Synthesis, characterization, and gene transfer application of poly(ethylene glycol-b-ethylenimine) with high molar mass polyamine block. , 2006, Biomacromolecules.

[6]  Nathan F. Bouxsein,et al.  Dendritic cationic lipids with highly charged headgroups for efficient gene delivery. , 2006, Bioconjugate chemistry.

[7]  F. Diederich,et al.  Effects of structural modification on gene transfection and self-assembling properties of amphiphilic dendrimers. , 2006, Organic & biomolecular chemistry.

[8]  S. Nguyen,et al.  High-density doxorubicin-conjugated polymeric nanoparticles via ring-opening metathesis polymerization. , 2005, Chemical communications.

[9]  F. Szoka,et al.  In vitro and in vivo evaluation of hydrophilic dendronized linear polymers. , 2005, Bioconjugate chemistry.

[10]  K. Leong,et al.  In vitro gene delivery using polyamidoamine dendrimers with a trimesyl core. , 2005, Biomacromolecules.

[11]  W. Binder,et al.  Combining Ring-Opening Metathesis Polymerization (ROMP) with Sharpless-Type “Click” Reactions: An Easy Method for the Preparation of Side Chain Functionalized Poly(oxynorbornenes) , 2004 .

[12]  S. Nguyen,et al.  Indomethacin-Containing Nanoparticles Derived from Amphiphilic Polynorbornene: A Model ROMP-Based Drug Encapsulation System , 2004 .

[13]  I. Biaggio,et al.  Synthesis and properties of a ROMP backbone polymer with efficient, laterally appended nonlinear optical chromophoresElectronic Supplementary Material (ESI): Full details of the synthesis of polymer 1 and comparison of the 1H-NMR spectra of 1 and monomer 2. See http://www.rsc.org/suppdata/jm/b3/b314 , 2004 .

[14]  R. Duncan.  The dawning era of polymer therapeutics , 2003, Nature Reviews Drug Discovery.

[15]  F. Diederich,et al.  Amphiphilic dendrimers: novel self-assembling vectors for efficient gene delivery. , 2003, Angewandte Chemie.

[16]  C Russell Middaugh,et al.  Barriers to nonviral gene delivery. , 2003, Journal of pharmaceutical sciences.

[17]  F. Ozawa,et al.  Convenient Route to Fischer-Type Carbene Ruthenium Complexes: Highly Selective Catalysts for Ring Opening/Cross-Metathesis of Norbornene Derivatives , 2003 .

[18]  Luke G Green,et al.  A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective "ligation" of azides and terminal alkynes. , 2002, Angewandte Chemie.

[19]  Clive J Roberts,et al.  Polyethylenimine-graft-poly(ethylene glycol) copolymers: influence of copolymer block structure on DNA complexation and biological activities as gene delivery system. , 2002, Bioconjugate chemistry.

[20]  J. Rabe,et al.  Molecular Structure of Single DNA Complexes with Positively Charged Dendronized Polymers , 2002 .

[21]  R. Grubbs,et al.  Metathesis of Electron-Rich Olefins: Structure and Reactivity of Electron-Rich Carbene Complexes , 2002 .

[22]  Kazunori Kataoka,et al.  Block copolymer micelles for delivery of gene and related compounds. , 2002, Advanced drug delivery reviews.

[23]  Dennis E. Discher,et al.  Polymer vesicles : Materials science: Soft surfaces , 2002 .

[24]  R. Grubbs,et al.  Mechanism and activity of ruthenium olefin metathesis catalysts. , 2001, Journal of the American Chemical Society.

[25]  Andrew D. Miller.  Cationic Liposomes for Gene Therapy , 1998 .

[26]  Atsushi Harada,et al.  Spontaneous Formation of Polyion Complex Micelles with Narrow Distribution from Antisense Oligonucleotide and Cationic Block Copolymer in Physiological Saline , 1996 .