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siRNA delivery with chitosan nanoparticles: Molecular properties favoring efficient gene silencing

Authors
Journal
Journal of Controlled Release
0168-3659
Publisher
Elsevier
Publication Date
Volume
158
Issue
2
Identifiers
DOI: 10.1016/j.jconrel.2011.11.012
Keywords
  • Chitosan
  • Sirna
  • Nanoparticles
  • Chain Length
  • Chain Architecture
Disciplines
  • Biology
  • Chemistry

Abstract

Abstract Chitosan has gained increasing interest for siRNA delivery. Although chitosan covers a family of structurally different polysaccharides, most siRNA delivery studies have been performed with conventional partially N-acetylated chitosans. Herein, the purpose was to identify fundamental chitosan molecular properties favoring siRNA delivery and efficient gene silencing in mammalian cells. Nanoparticles were prepared from well-defined chitosans of various chemical compositions, degrees of polymerization (DPn) and chain architectures. Structure-activity relationships were determined by the cellular uptake of siRNA and the knockdown efficiency at mRNA and protein levels. Additionally, the nanoparticle cytotoxicity was evaluated on the basis of cellular metabolic activity and membrane integrity. Our results show that the most efficient gene silencing was achieved using fully de-N-acetylated chitosans with intermediate chain lengths (DPn 100–300). These chitosans mediated efficient siRNA delivery at low siRNA concentrations and, in several cell lines, potent long-term silencing of both exogenous and endogenous target genes, with minimal cytotoxicity.

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