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Issue 13, 2014
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Untying a nanoscale knotted polymer structure to linear chains for efficient gene delivery in vitro and to the brain

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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 compared to 25 kDa-PEI (48-fold), SuperFect® (39-fold) and Lipofectamine®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 a platform transfection technology which should be investigated further for neurodegenerative disease therapies.

Graphical abstract: Untying a nanoscale knotted polymer structure to linear chains for efficient gene delivery in vitro and to the brain

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Supplementary files

Article information


Submitted
19 Dec 2013
Accepted
15 Apr 2014
First published
17 Apr 2014

Nanoscale, 2014,6, 7526-7533
Article type
Paper
Author version available

Untying a nanoscale knotted polymer structure to linear chains for efficient gene delivery in vitro and to the brain

B. Newland, A. Aied, A. V. Pinoncely, Y. Zheng, T. Zhao, H. Zhang, R. Niemeier, E. Dowd, A. Pandit and W. Wang, Nanoscale, 2014, 6, 7526
DOI: 10.1039/C3NR06737H

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