title: Tailoring the Surface of a Gene Delivery Vector with Carboxymethylated Dextran: A Systematic Analysis.
abstract: Polymeric nanocarriers are attractive nonviral vectors for gene delivery purposes in vivo. For such applications, numerous physiological and subcellular bottlenecks have to be overcome. In that endeavor, each structural feature of nanocarriers can be optimized with respect to its corresponding challenges. Here, we focused on the interface between a model gene delivery nanocarrier and relevant constituents of the physiological environment. We screened a library of carboxymethylated dextrans (CMD) for the electrostatic coating of positively charged nanocarriers. We evaluated the jointed influence of the CMD molecular weight and charge density upon nanocarrier coating with respect to DNase, small ions, plasma proteins, red blood cells, and target cells. A total of 4 out of 26 CMD coated nanocarriers successfully passed every screening assay, but did not yield increased reporter gene expression in target cells compared to uncoated nanocarriers. The fine-tuning of CMD for nanocarrier coating yielded a relevant shortlist of candidates that will be further tested in vivo.
authors: †Department of Chemical Engineering, Groupe de Recherche en Sciences et Technologies Biomédicales (GRSTB), École Polytechnique de Montréal, P.O. Box 6079, succ. Centre-Ville, Montreal (QC), Canada H3C 3A7.|‡Life Sciences | NRC Human Health Therapeutics Portfolio, Building Montreal-Royalmount, National Research Council Canada, Montreal (QC), Canada H4P 2R2.
authors: Charles
authors: C
authors: Fortier
authors: ‡Life Sciences | NRC Human Health Therapeutics Portfolio, Building Montreal-Royalmount, National Research Council Canada, Montreal (QC), Canada H4P 2R2.|§Département de Biochimie et Médecine Moléculaire, Université de Montréal, Montréal (QC), Canada H3C 3J7.
authors: Elodie
authors: E
authors: Louvier
authors: ‡Life Sciences | NRC Human Health Therapeutics Portfolio, Building Montreal-Royalmount, National Research Council Canada, Montreal (QC), Canada H4P 2R2.|§Département de Biochimie et Médecine Moléculaire, Université de Montréal, Montréal (QC), Canada H3C 3J7.
authors: Yves
authors: Y
authors: Durocher
authors: †Department of Chemical Engineering, Groupe de Recherche en Sciences et Technologies Biomédicales (GRSTB), École Polytechnique de Montréal, P.O. Box 6079, succ. Centre-Ville, Montreal (QC), Canada H3C 3A7.
authors: Gregory
authors: G
authors: De Crescenzo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003911:Dextrans / Q000009:adverse effects / Q000737:chemistry*; D004912:Erythrocytes / Q000187:drug effects; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D053769:Nanocapsules / Q000737:chemistry*; D012756:Sheep; D055672:Static Electricity
chemical_list: D003911:Dextrans; D053769:Nanocapsules; C014392:carboxymethyl dextran