title: VEGF-targeted magnetic nanoparticles for MRI visualization of brain tumor.
abstract: This work is focused on synthesis and characterization of targeted magnetic nanoparticles as magnetic resonance imaging (МRI) agents for in vivo visualization of gliomas. Ferric oxide (Fe3O4) cores were synthesized by thermal decomposition and coated with bovine serum albumin (BSA) to form nanoparticles with Deff of 53±9nm. The BSA was further cross-linked to improve colloidal stability. Monoclonal antibodies against vascular endothelial growth factor (mAbVEGF) were covalently conjugated to BSA through a polyethyleneglycol linker. Here we demonstrate that 1) BSA coated nanoparticles are stable and non-toxic to different cells at concentration up to 2.5mg/mL; 2) conjugation of monoclonal antibodies to nanoparticles promotes their binding to VEGF-positive glioma С6 cells in vitro; 3) targeted nanoparticles are effective in MRI visualization of the intracranial glioma. Thus, mAbVEGF-targeted BSA-coated magnetic nanoparticles are promising MRI contrast agents for glioma visualization.
  
  
  BACKGROUND
  This work focuses on synthesis and characterization of targeted magnetic nanoparticles as magnetic resonance imaging (МRI) agents for in vivo visualization of gliomas. The authors utilize the fact that high-grade gliomas have extensive areas of necrosis and hypoxia, which results in increased secretion of angiogenesis vascular endothelial growth factor (VEGF). Monoclonal antibodies against vascular endothelial growth factor (mAbVEGF) were covalently conjugated to crosslinked BSA coated ferric oxide (Fe3O4) nanoparticles. The results show that these targeted nanoparticles are effective in MRI visualization of the intracranial glioma and may provide a new and promising contrast agent.
authors: Department of Medical Nanobiotechnology, Pirogov Russian National Research Medical University, Moscow, Russia; Laboratory of Chemical Design of Bionanomaterials, Chemistry Department, M.V. Lomonosov Moscow State University, Moscow, Russia. Electronic address: abakumov1988@gmail.com.
authors: Maxim A
authors: MA
authors: Abakumov
authors: Department of Medical Nanobiotechnology, Pirogov Russian National Research Medical University, Moscow, Russia; Division of Fundamental and Applied Neurobiology, Serbsky State Research Center of Social and Forensic Psychiatry, Moscow, Russia; Laboratory of Chemical Design of Bionanomaterials, Chemistry Department, M.V. Lomonosov Moscow State University, Moscow, Russia.
authors: Natalia V
authors: NV
authors: Nukolova
authors: Center for Nanotechnology in Drug Delivery and Division of Molecular Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Marina
authors: M
authors: Sokolsky-Papkov
authors: Division of Fundamental and Applied Neurobiology, Serbsky State Research Center of Social and Forensic Psychiatry, Moscow, Russia.
authors: Sergey A
authors: SA
authors: Shein
authors: Division of Fundamental and Applied Neurobiology, Serbsky State Research Center of Social and Forensic Psychiatry, Moscow, Russia.
authors: Tatiana O
authors: TO
authors: Sandalova
authors: Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA; Center for Nanotechnology in Drug Delivery and Division of Molecular Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Hemant M
authors: HM
authors: Vishwasrao
authors: Center for Nanotechnology in Drug Delivery and Division of Molecular Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Nadezhda F
authors: NF
authors: Grinenko
authors: Department of Medical Nanobiotechnology, Pirogov Russian National Research Medical University, Moscow, Russia.
authors: Iliya L
authors: IL
authors: Gubsky
authors: Electron Microscopy for Materials Science (EMAT), University of Antwerp, Groenenborgerlaan 171, Belgium.
authors: Artem M
authors: AM
authors: Abakumov
authors: Laboratory of Chemical Design of Bionanomaterials, Chemistry Department, M.V. Lomonosov Moscow State University, Moscow, Russia; Center for Nanotechnology in Drug Delivery and Division of Molecular Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Alexander V
authors: AV
authors: Kabanov
authors: Department of Medical Nanobiotechnology, Pirogov Russian National Research Medical University, Moscow, Russia; Division of Fundamental and Applied Neurobiology, Serbsky State Research Center of Social and Forensic Psychiatry, Moscow, Russia.
authors: Vladimir P
authors: VP
authors: Chekhonin
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000737:chemistry / Q000494:pharmacology; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D002417:Cattle; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology; D005910:Glioma / Q000000981:diagnostic imaging* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D003287:Contrast Media; D058185:Magnetite Nanoparticles; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat
keywords: Glioblastoma; Iron oxide nanoparticles; MRI; VEGF