title: Multiscale investigation of USPIO nanoparticles in atherosclerotic plaques and their catabolism and storage in vivo.
abstract: The storage and catabolism of Ultrasmall SuperParamagnetic Iron Oxide (USPIO) nanoparticles were analyzed through a multiscale approach combining Two Photon Laser Scanning Microscopy (TPLSM) and High-Resolution Transmission Electron Microscopy (HRTEM) at different times after intravenous injection in an atherosclerotic ApoE(-/-) mouse model. The atherosclerotic plaque features and the USPIO heterogeneous biodistribution were revealed down from organ's scale to subcellular level. The biotransformation of the nanoparticle iron oxide (maghemite) core into ferritin, the non-toxic form of iron storage, was demonstrated for the first time ex vivo in atherosclerotic plaques as well as in spleen, the iron storage organ. These results rely on an innovative spatial and structural investigation of USPIO's catabolism in cellular phagolysosomes. This study showed that these nanoparticles were stored as non-toxic iron compounds: maghemite oxide or ferritin, which is promising for MRI detection of atherosclerotic plaques in clinics using these USPIOs. From the Clinical Editor: Advance in nanotechnology has brought new contrast agents for clinical imaging. In this article, the authors investigated the use and biotransformation of Ultrasmall Super-paramagnetic Iron Oxide (USPIO) nanoparticles for analysis of atherosclerotic plagues in Two Photon Laser Scanning Microscopy (TPLSM) and High-Resolution Transmission Electron Microscopy (HRTEM). The biophysical data generated from this study could enable the possible use of these nanoparticles for the benefits of clinical patients.
authors.affiliation: Institut Lumière Matière, UMR 5306 Université Claude Bernard Lyon1-CNRS, Université de Lyon, Villeurbanne, Cedex, France; National Institute of Materials Physics, Magurele, Bucharest, Romania.
authors.forename: Valentin-Adrian
authors.initials: VA
authors.lastname: Maraloiu
authors.affiliation: Two-Photon Microscopy Platform, IBiSA-ISdV, Grenoble Institute of Neuroscience INSERM U836, UJF, Grenoble, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Appaix
authors.affiliation: Radiopharmaceutiques Biocliniques Lab., Faculté de Médecine, La Tronche, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Broisat
authors.affiliation: Institut de Biologie et Chimie des Protéines, LBTI, UMR 5305, CNRS/University of Lyon 1, Lyon, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Le Guellec
authors.affiliation: National Institute of Materials Physics, Magurele, Bucharest, Romania.
authors.forename: Valentin Serban
authors.initials: VS
authors.lastname: Teodorescu
authors.affiliation: Radiopharmaceutiques Biocliniques Lab., Faculté de Médecine, La Tronche, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Ghezzi
authors.affiliation: Clinatec, INSERM UA 01, Grenoble, France. Electronic address: Boudewijn.vandersanden@ujf-grenoble.fr.
authors.forename: Boudewijn
authors.initials: B
authors.lastname: van der Sanden
authors.affiliation: Institut Lumière Matière, UMR 5306 Université Claude Bernard Lyon1-CNRS, Université de Lyon, Villeurbanne, Cedex, France. Electronic address: Marie-Genevieve.Blanchin@univ-lyon1.fr.
authors.forename: Marie-Genevieve
authors.initials: MG
authors.lastname: Blanchin
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics; D003911:Dextrans / Q000493:pharmacokinetics*; D058185:Magnetite Nanoparticles; D008422:Materials Testing; D008657:Metabolic Clearance Rate; D008660:Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission / Q000379:methods; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D013347:Subcellular Fractions / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; C097921:ferumoxtran-10
keywords: Atherotic plaque; MRI contrast agent; TEM; Two-photon laser scanning microscopy and nanotechnology; USPIO nanoparticles