Untying a nanoscale knotted polymer structure to linear chains for efficient gene delivery in vitro and to the brain
Newland, B. Aied, A. Pinoncely, A. V. Zheng, Y. Zhao, T. Zhang, H. Niemeier, R. Dowd, E. Pandit, A. Wang, W.
Newland, B.
Aied, A.
Pinoncely, A. V.
Zheng, Y.
Zhao, T.
Zhang, H.
Niemeier, R.
Dowd, E.
Pandit, A.
Wang, W.
Repository DOI
Publication Date
2014-01-01
Type
Article
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Citation
Newland, B. Aied, A.; Pinoncely, A. V.; Zheng, Y.; Zhao, T.; Zhang, H.; Niemeier, R.; Dowd, E.; Pandit, A.; Wang, W. (2014). Untying a nanoscale knotted polymer structure to linear chains for efficient gene delivery in vitro and to the brain. Nanoscale 6 (13), 7526-7533
Abstract
The purpose of this study was to develop a platform transfection technology, for applications in the brain, which could transfect astrocytes without requiring cell specific functionalization and without the common cause of toxicity through high charge density. Here we show that a simple and scalable preparation technique can be used to produce a "knot" structured cationic polymer, where single growing chains can crosslink together via disulphide intramolecular crosslinks (internal cyclizations). This well-defined knot structure can thus "untie" under reducing conditions, showing a more favorable transfection profile for astrocytes comp-red to 25 kDa-PEI (48-fold), SuperFect (R) (39-fold) and Lipofectamine (R) 2000 (18-fold) whilst maintaining neural cell viability at over 80% after four days of culture. The high transfection/lack of toxicity of this knot structured polymer in vitro, combined with its ability to mediate luciferase transgene expression in the adult rat brain, demonstrates its use as - platform transfection technology which should be investigated further for neurodegenerative disease therapies.
Funder
Publisher
Royal Society of Chemistry (RSC)
Publisher DOI
10.1039/c3nr06737h
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Attribution-NonCommercial-NoDerivs 3.0 Ireland