title: A versatile coiled-coil tethering system for the oriented display of ligands on nanocarriers for targeted gene delivery.
abstract: Surface 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.
authors.affiliation: Department of Chemical Engineering, Groupe de Recherche en Sciences et Technologie Biomédicales, Bio-P2 Research Unit, École Polytechnique de Montréal, P.O. Box 6079, succ. Centre-Ville, Montreal, QC, Canada H3C 3A7.
authors.forename: Charles
authors.initials: C
authors.lastname: Fortier
authors.forename: Gregory
authors.initials: G
authors.lastname: De Crescenzo
authors.forename: Yves
authors.initials: Y
authors.lastname: Durocher
mesh_terms: D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D018390:Gene Targeting; D006801:Humans; D008024:Ligands; D008175:Lung Neoplasms / Q000235:genetics*; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D008024:Ligands; D053769:Nanocapsules; D011094:Polyethyleneimine; D004247:DNA; D066246:ErbB Receptors