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Hyperbranched polymers as delivery vectors for oligonucleotides

Authors

  • Jian Hong Tan,

    1. Australian Institute for Bioengineering and Nanotechnology, and Centre for Advanced Imaging, The University of Queensland, St. Lucia, Queensland 4072, Australia
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  • Nigel A. J. McMillan,

    1. School of Medical Sciences, Griffith University, Southport, Queensland 4222, Australia
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  • Elizabeth Payne,

    1. The University of Queensland Diamantina Institute, The University of Queensland, Research Wing, Building 1 Princess Alexandra Hospital, Woolloongabba, Queensland 4102, Australia
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  • Cameron Alexander,

    1. School of Pharmacy, The University of Nottingham, Nottingham NG7 2RD, United Kingdom
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  • Felicity Heath,

    1. School of Pharmacy, The University of Nottingham, Nottingham NG7 2RD, United Kingdom
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  • Andrew K. Whittaker,

    1. Australian Institute for Bioengineering and Nanotechnology, and Centre for Advanced Imaging, The University of Queensland, St. Lucia, Queensland 4072, Australia
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  • Kristofer J. Thurecht

    Corresponding author
    1. Australian Institute for Bioengineering and Nanotechnology, and Centre for Advanced Imaging, The University of Queensland, St. Lucia, Queensland 4072, Australia
    • Australian Institute for Bioengineering and Nanotechnology, Centre for Advance Imaging, The University of Queensland, St. Lucia, Queensland 4072, Australia
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Abstract

We report on the synthesis and characterization of hyperbranched dimethylaminoethyl methacrylate (DMAEMA) polymers using reversible addition fragmentation chain transfer polymerization. These polymers are unimolecular and globular and hence interact differently with DNA than conventional DMAEMA or block copolymers. The polymers were shown to effectively bind and condense oligonucleotides (ODNs); visualization of the bound complexes was achieved using atomic force microscopy, whereas isothermal titration calorimetry described the thermodynamics of binding. The ODNs were effectively protected from enzymatic degradation (DNAses) when condensed by all the polycations studied. However, internalization of the complexes into HeLa cells was less effective when the polycation was chain extended with polyethyleneglycol monomethylether methacrylate. Conjugation of folic acid to the periphery of the polycation facilitated much enhanced uptake of the oligomeric DNA into the HeLa cells due to overexpression of folate receptors on the surface of HeLa cells. Although significant cytotoxicity was observed at high polymer concentrations, this could be alleviated by shielding of the polycation using poly(ethyleneglycol monomethylether methacrylate). These results suggest that hyperbranched polymers formed in this way exhibit interesting complexation behavior with ODNs and thus are promising models to study as gene delivery vectors. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012

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