title: Single-walled carbon nanotubes noncovalently functionalized with lipid modified polyethylenimine for siRNA delivery in vitro and in vivo.
abstract: siRNA can downregulate the expression of specific genes. However, delivery to specific cells and tissues in vivo presents significant challenges. Modified carbon nanotubes (CNTs) have been shown to protect siRNA and facilitate its entry into cells. However, simple and efficient methods to functionalize CNTs are needed. Here, noncovalent functionalization of CNTs is performed and shown to effectively deliver siRNA to target cells. Specifically, single-walled CNTs were functionalized by noncovalent association with a lipopolymer. The lipopolymer (DSPE-PEG) was composed of a phospholipid 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) and poly(ethylene glycol) (PEG). Three different ratios of polyethylenimine (PEI) to DSPE-PEG were synthesized and characterized and the products were used to disperse CNTs. The resulting materials were used for siRNA delivery in vitro and in vivo. The structural, biophysical, and biological properties of DGI/C and their complexes formed with siRNA were investigated. Cytotoxicity of the materials was low, and effective gene silencing in B16-F10 cells was demonstrated in vitro. In addition, significant uptake of siRNA as well as gene silencing in the liver was found following intravenous injection. This approach provides a new strategy for siRNA delivery and could provide insight for the development of noncovalently functionalized CNTs for siRNA therapy.
authors.affiliation: Departments of Pathology, Surgery, Oncology, Microbiology and Immunology, Physiology and Pharmacology and ∥Department of Chemistry, Chemical and Biochemical Engineering, University of Western Ontario , London, Ontario N6A 5H5, Canada.
authors.forename: King S
authors.initials: KS
authors.lastname: Siu
authors.forename: Xiufen
authors.initials: X
authors.lastname: Zheng
authors.forename: Yanling
authors.initials: Y
authors.lastname: Liu
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xusheng
authors.initials: X
authors.lastname: Zhang
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.forename: Ken
authors.initials: K
authors.lastname: Yuan
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Gillies
authors.forename: James
authors.initials: J
authors.lastname: Koropatnick
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Min
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D037742:Nanotubes, Carbon / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D014162:Transfection
chemical_list: D037742:Nanotubes, Carbon; D010714:Phosphatidylethanolamines; D034741:RNA, Small Interfering; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D011094:Polyethyleneimine