title: Targeted delivery of liposomal nanocontainers to the peritumoral zone of glioma by means of monoclonal antibodies against GFAP and the extracellular loop of Cx43.
abstract: The selectivity of PEGylated immunoliposomes based on monoclonal antibodies against GFAP and the E2 extracellular loop of connexin 43 (MAbE2Cx43) with respect to the focus of a glioma was estimated in experiments on animals with intracranial C6 glioma. Stealth immunoliposomes were labeled with 2 alternative labels, a fluorescent (Dil C18) and a paramagnetic (Gd-DTPA) one. Fluorescent-labeled liposomal nanocontainers were detected at the periphery of the glioma, where the target antigens were overexpressed, 48 hours after injection. Dynamic T1 MRI of rats injected with paramagnetic immunoliposomes carrying MAbE2Cx43 showed distinct accumulation of the paramagnetic contrast agent at the periphery of the glioma, which began 6 hours after administration. These data suggest that immunoliposomal nanocontainers based on antibodies against GFAP and the E2 extracellular fragment of connexin 43 are suitable for targeted delivery of diagnostic and therapeutic drugs to the peritumoral invasion zone of high-grade gliomas.
  
  
  BACKGROUND
  PEGylated immunoliposomes based on monoclonal antibodies against GFAP and the E2 extracellular loop of connexin 43 were investigated in animals with intracranial C6 glioma. These immunoliposomal nanocontainers were found suitable for targeted delivery of diagnostic and therapeutic drugs to the peritumoral invasion zone of high-grade gliomas.
authors.affiliation: Department of Fundamental and Applied Neurobiology, Serbsky National Research Center for Social and Forensic Psychiatry, Ministry of Health and Social Development of the Russian Federation, Moscow, Russia.
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Chekhonin
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Baklaushev
authors.forename: Gaukhar M
authors.initials: GM
authors.lastname: Yusubalieva
authors.forename: Anastasia E
authors.initials: AE
authors.lastname: Belorusova
authors.forename: Michael V
authors.initials: MV
authors.lastname: Gulyaev
authors.forename: Eugene B
authors.initials: EB
authors.lastname: Tsitrin
authors.forename: Nadezhda F
authors.initials: NF
authors.lastname: Grinenko
authors.forename: Olga I
authors.initials: OI
authors.lastname: Gurina
authors.forename: Yuriy A
authors.initials: YA
authors.lastname: Pirogov
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology*; D018031:Connexin 43 / Q000276:immunology; D004337:Drug Carriers / Q000138:chemical synthesis; D005260:Female; D019786:Gadolinium DTPA / Q000737:chemistry; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology; D005910:Glioma / Q000276:immunology / Q000473:pathology*; D008081:Liposomes / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000276:immunology*; D008279:Magnetic Resonance Imaging; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000276:immunology; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats
chemical_list: D000911:Antibodies, Monoclonal; D018031:Connexin 43; D004337:Drug Carriers; D005904:Glial Fibrillary Acidic Protein; D008081:Liposomes; D011092:Polyethylene Glycols; D019786:Gadolinium DTPA