title: siRNA delivery with chitosan nanoparticles: Molecular properties favoring efficient gene silencing.
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 (DP(n)) 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 (DP(n) 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.
authors: Norwegian Biopolymer Laboratory (NOBIPOL), Department of Biotechnology, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway.
authors: Jostein
authors: J
authors: Malmo
authors: Hanne
authors: H
authors: Sørgård
authors: Kjell M
authors: KM
authors: Vårum
authors: Sabina P
authors: SP
authors: Strand
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage*; D004337:Drug Carriers / Q000008:administration & dosage*; D020868:Gene Silencing; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage*; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D014162:Transfection / Q000379:methods
chemical_list: D004337:Drug Carriers; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D048271:Chitosan; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+)