Hyperbranched polymers as delivery vectors for oligonucleotides

Tan, Jian Hong, McMillan, Nigel A. J., Payne, Elizabeth, Alexander, Cameron, Heath, Felicity, Whittaker, Andrew K. and Thurecht, Kristofer J. (2012) Hyperbranched polymers as delivery vectors for oligonucleotides. Journal of Polymer Science Part A: Polymer Chemistry, 50 13: 2585-2595.


Author Tan, Jian Hong
McMillan, Nigel A. J.
Payne, Elizabeth
Alexander, Cameron
Heath, Felicity
Whittaker, Andrew K.
Thurecht, Kristofer J.
Title Hyperbranched polymers as delivery vectors for oligonucleotides
Journal name Journal of Polymer Science Part A: Polymer Chemistry   Check publisher's open access policy
ISSN 0887-624X
1099-0518
Publication date 2012
Sub-type Article (original research)
DOI 10.1002/pola.26055
Volume 50
Issue 13
Start page 2585
End page 2595
Total pages 11
Place of publication Hoboken NJ, United States
Publisher John Wiley & Sons
Collection year 2013
Language eng
Formatted 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.
Keyword Biomaterials
Branched
Cationic polymer
Gene delivery
Hyperbranched polymer
Isothermal calorimetry
RAFT polymerization
Reversible addition fragmentation chain transfer (RAFT)
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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Created: Mon, 14 May 2012, 16:27:40 EST by Sandrine Ducrot on behalf of Aust Institute for Bioengineering & Nanotechnology