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Polymers 2018, 10(6), 687; https://doi.org/10.3390/polym10060687

Modular Synthesis of Bioreducible Gene Vectors through Polyaddition of N,N′-Dimethylcystamine and Diglycidyl Ethers

1
Department of Biomolecular Nanotechnology, MESA+ Institute for Nanotechnology and TechMed Institute for Health and Biomedical Technologies, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands
2
20Med Therapeutics, Zuidhorst 251, Drienerlolaan 5, 7522 NB Enschede, The Netherlands
3
Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 4 May 2018 / Revised: 13 June 2018 / Accepted: 16 June 2018 / Published: 20 June 2018
(This article belongs to the Special Issue Polymers in Gene Delivery)
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Abstract

Bioreducible, cationic linear poly(amino ether)s (PAEs) were designed as promising gene vectors. These polymers were synthesized by the reaction of a disulfide-functional monomer, N,N′-dimethylcystamine (DMC), and several different diglycidyl ethers. The resulting PAEs displayed a substantial buffer capacity (up to 64%) in the endosomal acidification region of pH 7.4–5.1. The PAEs condense plasmid DNA into 80–200 nm sized polyplexes, and have surface charges ranging from +20 to +40 mV. The polyplexes readily release DNA upon exposure to reducing conditions (2.5 mM DTT) due to the cleavage of the disulfide groups that is present in the main chain of the polymers, as was demonstrated by agarose gel electrophoresis. Upon exposing COS-7 cells to polyplexes that were prepared at polymer/DNA w/w ratios below 48, cell viabilities between 80–100% were observed, even under serum-free conditions. These polyplexes show comparable or higher transfection efficiencies (up to 38%) compared to 25 kDa branched polyethylenimine (PEI) polyplexes (12% under serum-free conditions). Moreover, the PAE-based polyplexes yield transfection efficiencies as high as 32% in serum-containing medium, which makes these polymers interesting for gene delivery applications. View Full-Text
Keywords: cationic polymers; epoxy-amine reaction; bioreducible; gene delivery; disulfides; poly(amino ether)s cationic polymers; epoxy-amine reaction; bioreducible; gene delivery; disulfides; poly(amino ether)s
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Si, G.; Elzes, M.R.; Engbersen, J.F.J.; Paulusse, J.M.J. Modular Synthesis of Bioreducible Gene Vectors through Polyaddition of N,N′-Dimethylcystamine and Diglycidyl Ethers. Polymers 2018, 10, 687.

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