title: Tumor targeting using magnetic nanoparticle Hsp70 conjugate in a model of C6 glioma.
abstract: BACKGROUND
  Superparamagnetic iron oxide nanoparticles (SPIONs), due to their unique magnetic properties, have the ability to function both as magnetic resonance (MR) contrast agents, and can be used for thermotherapy. SPIONs conjugated to the heat shock protein Hsp70 that selectively binds to the CD40 receptor present on glioma cells, could be used for MR contrast enhancement of experimental C6 glioma.
  
  
  METHODS
  The magnetic properties of the Hsp70-SPIONs were measured by NMR relaxometry method. The uptake of nanoparticles was assessed on the C6 glioma cells by confocal and electron microscopes. The tumor selectivity of Hsp70-SPIONs being intravenously administered was analyzed in the experimental model of C6 glioma in the MRI scanner.
  
  
  RESULTS
  Hsp70-SPIONs relaxivity corresponded to the properties of negative contrast agents with a hypointensive change of resonance signal in MR imaging. A significant accumulation of the Hsp70-SPIONs but not the non-conjugated nanoparticles was observed by confocal microscopy within C6 cells. Negative contrast tumor enhancement in the T2-weighted MR images was higher in the case of Hsp70-SPIONs in comparison to non-modified SPIONs. Histological analysis of the brain sections confirmed the retention of the Hsp70-SPIONs in the glioma tumor but not in the adjacent normal brain tissues.
  
  
  CONCLUSIONS
  The study demonstrated that Hsp70-SPION conjugate intravenously administered in C6 glioma model accumulated in the tumors and enhanced the contrast of their MR images.
authors.affiliation: Corresponding author: Maxim A. Shevtsov, MD, PhD, Laboratory of Cell Protection Mechanisms, Institute of Cytology of Russian Academy of Sciences, Tikhoretsky Ave. 4, 194064, St. Petersburg, Russia. shevtsov-max@mail.ru.
authors.forename: Maxim A
authors.initials: MA
authors.lastname: Shevtsov
authors.forename: Ludmila Y
authors.initials: LY
authors.lastname: Yakovleva
authors.forename: Boris P
authors.initials: BP
authors.lastname: Nikolaev
authors.forename: Yaroslav Y
authors.initials: YY
authors.lastname: Marchenko
authors.forename: Anatolii V
authors.initials: AV
authors.lastname: Dobrodumov
authors.forename: Kirill V
authors.initials: KV
authors.lastname: Onokhin
authors.forename: Yana S
authors.initials: YS
authors.lastname: Onokhina
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Selkov
authors.forename: Anastasiia L
authors.initials: AL
authors.lastname: Mikhrina
authors.forename: Irina V
authors.initials: IV
authors.lastname: Guzhova
authors.forename: Marina G
authors.initials: MG
authors.lastname: Martynova
authors.forename: Olga A
authors.initials: OA
authors.lastname: Bystrova
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Ischenko
authors.forename: Boris A
authors.initials: BA
authors.lastname: Margulis
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D018840:HSP70 Heat-Shock Proteins; D058185:Magnetite Nanoparticles; D011994:Recombinant Proteins
keywords: Hsp70; SPION; glioma; magnetic nanoparticles; targeted delivery