title: Low molecular weight chitosan conjugated with folate for siRNA delivery in vitro: optimization studies.
abstract: The low transfection efficiency of chitosan is one of its drawbacks as a gene delivery carrier. Low molecular weight chitosan may help to form small-sized polymer-DNA or small interfering RNA (siRNA) complexes. Folate conjugation may improve gene transfection efficiency because of the promoted uptake of folate receptor-bearing cells. In the present study, chitosan was conjugated with folate and investigated for its efficacy as a delivery vector for siRNA in vitro. We demonstrate that the molecular weight of chitosan has a major influence on its biological and physicochemical properties, and very low molecular weight chitosan (below 10 kDa) has difficulty in forming stable complexes with siRNA. In this study, chitosan 25 kDa and 50 kDa completely absorbed siRNA and formed nanoparticles (≤220 nm) at a chitosan to siRNA weight ratio of 50:1. The introduction of a folate ligand onto chitosan decreased nanoparticle toxicity. Compared with chitosan-siRNA, folate-chitosan-siRNA nanoparticles improved gene silencing transfection efficiency. Therefore, folate-chitosan shows potential as a viable candidate vector for safe and efficient siRNA delivery.
authors.affiliation: Orthopaedics Research Laboratory, Research Centre, Sacré-Coeur Hospital, Montreal, Quebec, Canada.
authors.forename: Julio C
authors.initials: JC
authors.lastname: Fernandes
authors.forename: Xingping
authors.initials: X
authors.lastname: Qiu
authors.forename: Francoise M
authors.initials: FM
authors.lastname: Winnik
authors.forename: Mohamed
authors.initials: M
authors.lastname: Benderdour
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhang
authors.forename: Kerong
authors.initials: K
authors.lastname: Dai
authors.forename: Qin
authors.initials: Q
authors.lastname: Shi
mesh_terms: D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D005492:Folic Acid / Q000737:chemistry*; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D008970:Molecular Weight; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000235:genetics*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics*; D014162:Transfection / Q000379:methods*
chemical_list: D053769:Nanocapsules; D034741:RNA, Small Interfering; D048271:Chitosan; D005492:Folic Acid