title: Genetically tailored magnetosomes used as MRI probe for molecular imaging of brain tumor.
abstract: We investigate here the potential of single step production of genetically engineered magnetosomes, bacterial biogenic iron-oxide nanoparticles embedded in a lipid vesicle, as a new tailorable magnetic resonance molecular imaging probe. We demonstrate in vitro the specific binding and the significant internalization into U87 cells of magnetosomes decorated with RGD peptide. After injection at the tail vein of glioblastoma-bearing mice, we evidence in the first 2 h the rapid accumulation of both unlabeled and functionalized magnetosomes inside the tumor by Enhanced Permeability and Retention effects. 24 h after the injection, a specific enhancement of the tumor contrast is observed on MR images only for RGD-labeled magnetosomes. Post mortem acquisition of histological data confirms MRI results with more magnetosomes found into the tumor treated with functionalized magnetosomes. This work establishes the first proof-of-concept of a successful bio-integrated production of molecular imaging probe for MRI.
authors.affiliation: UNIRS, CEA/DRF/I(2)BM/NeuroSpin, CEA Saclay, Gif-sur-Yvette, France.
authors.forename: M
authors.initials: M
authors.lastname: Boucher
authors.affiliation: UNIRS, CEA/DRF/I(2)BM/NeuroSpin, CEA Saclay, Gif-sur-Yvette, France.
authors.forename: F
authors.initials: F
authors.lastname: Geffroy
authors.affiliation: LBC, CEA/DRF/BIAM, CEA Cadarache, Saint-Paul-lez-Durance, France; UMR 7265, Centre National de Recherche Scientifique, Saint-Paul-lez-Durance, France; Aix Marseille Université, Saint-Paul-lez-Durance, France.
authors.forename: S
authors.initials: S
authors.lastname: Prévéral
authors.affiliation: LI2D, CEA/DRF/IBITEC-S/SPI, CEA Marcoule, Bagnols-sur-Cèze, France.
authors.forename: L
authors.initials: L
authors.lastname: Bellanger
authors.affiliation: UNIRS, CEA/DRF/I(2)BM/NeuroSpin, CEA Saclay, Gif-sur-Yvette, France.
authors.forename: E
authors.initials: E
authors.lastname: Selingue
authors.affiliation: LBC, CEA/DRF/BIAM, CEA Cadarache, Saint-Paul-lez-Durance, France; UMR 7265, Centre National de Recherche Scientifique, Saint-Paul-lez-Durance, France; Aix Marseille Université, Saint-Paul-lez-Durance, France.
authors.forename: G
authors.initials: G
authors.lastname: Adryanczyk-Perrier
authors.affiliation: LBC, CEA/DRF/BIAM, CEA Cadarache, Saint-Paul-lez-Durance, France; UMR 7265, Centre National de Recherche Scientifique, Saint-Paul-lez-Durance, France; Aix Marseille Université, Saint-Paul-lez-Durance, France.
authors.forename: M
authors.initials: M
authors.lastname: Péan
authors.affiliation: LBC, CEA/DRF/BIAM, CEA Cadarache, Saint-Paul-lez-Durance, France; UMR 7265, Centre National de Recherche Scientifique, Saint-Paul-lez-Durance, France; Aix Marseille Université, Saint-Paul-lez-Durance, France.
authors.forename: C T
authors.initials: CT
authors.lastname: Lefèvre
authors.affiliation: LBC, CEA/DRF/BIAM, CEA Cadarache, Saint-Paul-lez-Durance, France; UMR 7265, Centre National de Recherche Scientifique, Saint-Paul-lez-Durance, France; Aix Marseille Université, Saint-Paul-lez-Durance, France.
authors.forename: D
authors.initials: D
authors.lastname: Pignol
authors.affiliation: LBC, CEA/DRF/BIAM, CEA Cadarache, Saint-Paul-lez-Durance, France; UMR 7265, Centre National de Recherche Scientifique, Saint-Paul-lez-Durance, France; Aix Marseille Université, Saint-Paul-lez-Durance, France; Aix Marseille Université, CNRS, Laboratoire de Chimie Bactérienne, Marseille, France.
authors.forename: N
authors.initials: N
authors.lastname: Ginet
authors.affiliation: UNIRS, CEA/DRF/I(2)BM/NeuroSpin, CEA Saclay, Gif-sur-Yvette, France. Electronic address: sebastien.meriaux@cea.fr.
authors.forename: S
authors.initials: S
authors.lastname: Mériaux
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry; D024861:Genetic Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods; D055944:Magnetosomes / Q000737:chemistry* / Q000235:genetics* / Q000648:ultrastructure; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D015336:Molecular Probe Techniques; D015335:Molecular Probes / Q000737:chemistry; D058726:Nanoconjugates / Q000737:chemistry / Q000648:ultrastructure; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D014408:Biomarkers, Tumor; D003287:Contrast Media; D015335:Molecular Probes; D058726:Nanoconjugates; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid
keywords: Biogenic nanoparticle; Functionalized magnetosome; Iron-oxide contrast agent; Magnetic resonance imaging; Molecular imaging of brain tumor