A versatile coiled-coil tethering system for the oriented display of ligands on nanocarriers for targeted gene delivery

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DOIResolve DOI: http://doi.org/10.1016/j.biomaterials.2012.10.047
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TypeArticle
Journal titleBiomaterials
ISSN0142-9612
Volume34
Issue4
Pages13441353; # of pages: 10
Subjecttransfection; polyethylenimine; non-viral vector; targeting; oriented tethering; epidermal growth factor (EGF)
AbstractSurface modification of non-viral gene delivery nanocarriers may provide advanced features such as receptor targeting, endosomal escape and nuclear import. We here report the design of a versatile and tunable immobilization protocol to functionalize nanocarriers for improved transient gene expression. Our strategy is based on specific interactions occurring between a coil-tagged ligand and a complementary coil-functionalized nanocarrier. As a proof of concept, targeting of DNA/polyethylenimine polyplexes to the epidermal growth factor receptor of A431 cells was investigated. Coiled-coil-mediated oriented tethering of epidermal growth factor triggered a drastic increase of the internalization rate of the targeted polyplexes. To explore the tunability of our platform, surface density of targeting ligand was varied; our results indicated that the internalization rate varied with the ligand-to-polyplex ratio in a “switch mode” fashion. This work prefigures possible avenues for our coiled-coil platform in multiplex functionalization to address transient gene expression bottlenecks in recombinant protein production.
Publication date
PublisherElsevier
LanguageEnglish
AffiliationHuman Health Therapeutics; National Research Council Canada
Peer reviewedYes
NRC number53182
NPARC number21268241
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Record identifier1c9e37f0-5368-46c5-8d02-fe1ea701247c
Record created2013-06-07
Record modified2016-05-09
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