title: siRNA associated with immunonanoparticles directed against cd99 antigen improves gene expression inhibition in vivo in Ewing's sarcoma.
abstract: Ewing's sarcoma is a rare, mostly pediatric bone cancer that presents a chromosome abnormality called EWS/Fli-1, responsible for the development of the tumor. In vivo, tumor growth can be inhibited specifically by delivering small interfering RNA (siRNA) associated with nanoparticles. The aim of the work was to design targeted nanoparticles against the cell membrane glycoprotein cd99, which is overexpressed in Ewing's sarcoma cells to improve siRNA delivery to tumor cells. Biotinylated poly(isobutylcyanoacrylate) nanoparticles were conceived as a platform to design targeted nanoparticles with biotinylated ligands and using the biotin-streptavidin coupling method. The targeted nanoparticles were validated in vivo for the targeted delivery of siRNA after systemic administration to mice bearing a tumor model of the Ewing's sarcoma. The expression of the gene responsible of Ewing's sarcoma was inhibited at 78% ± 6% by associating the siRNA with the cd99-targeted nanoparticles compared with an inhibition of only 41% ± 9% achieved with the nontargeted nanoparticles.
authors: CNRS UMR 8203 Vectorologie et thérapeutiques anticancéreuses, 114 rue Edouard Vaillant, 94805 Villejuif Cedex, France.
authors: A L
authors: AL
authors: Ramon
authors: J R
authors: JR
authors: Bertrand
authors: H
authors: H
authors: de Martimprey
authors: G
authors: G
authors: Bernard
authors: G
authors: G
authors: Ponchel
authors: C
authors: C
authors: Malvy
authors: C
authors: C
authors: Vauthier
mesh_terms: D000071443:12E7 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics*; D048271:Chitosan / Q000737:chemistry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D011108:Polymers / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000502:physiology; D012512:Sarcoma, Ewing / Q000378:metabolism* / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000071443:12E7 Antigen; D015703:Antigens, CD; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D011108:Polymers; D034741:RNA, Small Interfering; D048271:Chitosan