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Tailoring the surface of a gene delivery vector with carboxymethylated dextran: a systematic analysis

Par Conseil national de recherches du Canada

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DOITrouver le DOI : https://doi.org/10.1021/acs.biomac.5b00221
AuteurRechercher : 1; Rechercher : 2; Rechercher : 1; Rechercher :
Affiliation
  1. Conseil national de recherches du Canada. Thérapeutique en santé humaine
  2. Conseil national de recherches du Canada
FormatTexte, Article
Sujetdextran; electrostatic coatings; gene transfer; physiological models; carboxymethylated dextran; gene delivery vectors; physiological environment; polymeric nanocarriers; positively charged; reporter-gene expression; gene expression; carboxymethyldextran; deoxyribonuclease; nanocarrier; plasma protein; plasmid DNA; polymer; adsorption; erythrocyte; human cell; nanoencapsulation; nonviral gene delivery system; particle size; sheep; surface property; target cell
Résumé
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.
Date de publication
Maison d’éditionACS Publications
Dans
  • Biomacromolecules 16, nº 6 : 1671–1681.
Langueanglais
Publications évaluées par des pairsOui
Numéro du CNRCNRC-HHT-53291
Numéro NPARC21275803
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Identificateur de l’enregistrementab1c9b68-9dc8-474c-a7ca-0ed13201ac54
Enregistrement créé2015-07-14
Enregistrement modifié2020-06-02
Date de modification :