A direct comparison of linear and star-shaped poly(dimethylaminoethyl acrylate) polymers for polyplexation with DNA and cytotoxicity in cultured cell lines

Liao, Xin, Walden, Grace, Falcon, Noelia D, Donell, Simon, Raxworthy, Mike, Wormstone, Michael, Riley, Graham P and Saeed, Aram (2017) A direct comparison of linear and star-shaped poly(dimethylaminoethyl acrylate) polymers for polyplexation with DNA and cytotoxicity in cultured cell lines. European Polymer Journal, 87. 458–467. ISSN 0014-3057

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Abstract

Abstract Poly[2-(Dimethylamino) ethyl acrylate] (PDMAEA) based polymers have been studied as potential gene delivery system. However, few reports emerging in literature suggesting that star-shaped PDMAEA based polymers are performing better in polyplexation with DNA, cytotoxicity and transfection, as compared to linear counterparts. Nonetheless, little evidences exist on direct comparison between the linear and star-shaped polymer structures. To address this, a series of new star-shaped PDMAEA polymers with linear counterparts were synthesised and directly compared their polyplexation with DNA and cytotoxicity in culture cell lines. The star-shaped PDMAEA polymers were synthesised using pentaerythritol tetrakis [2-(dodecylthiocarbonothioylthio)-2-methylpropionate] (4-arm DDMAT) RAFT agent in a “core-first” approach, whereas 2-(dodecylthiocarbonothioylthio)-2-methylpropionate was used to synthesise linear PDMAEA polymers. In order to investigate the effect of molar mass, both star-shaped and linear PDMAEA were synthesised in low (10kDa) and high (20kDa) molar mass. It must be noted here that the overall molar mass of the star-shaped polymer was equal to that of the linear counterparts. Interestingly, we found that the star-shaped polymer has slightly smaller hydrodynamic diameter (more compact) relative to linear counterparts, and importantly, star-shaped PDMAEA binds to DNA at much lower nitrogen to phosphate ratio (N/P ratio). However, the cytotoxicity studies in cultured 3T3 murine cell lines demonstrated that both star-shaped and linear counterparts have no toxicity at low 10kDa, but significantly toxic at higher 20kDa molar mass, this finding confirmed that the molar mass of PDMAEA play a key role in cytotoxicity effect, not variable polymer structures. Taken together, star-shaped PDMAEA binds more effectively to DNA than linear counterparts and showed no toxicity at 10kDa molar mass at variable polymer concentrations.

Item Type: Article
Uncontrolled Keywords: cationic polymer,gene delivery,star-shaped polymer,cytotoxicity,polyplex
Faculty \ School: Faculty of Science > School of Pharmacy
Faculty of Science
Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Biological Sciences
Related URLs:
Depositing User: Pure Connector
Date Deposited: 24 Sep 2016 00:41
Last Modified: 25 Aug 2020 23:42
URI: https://ueaeprints.uea.ac.uk/id/eprint/60188
DOI: 10.1016/j.eurpolymj.2016.08.021

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