title: Ultrasmall Nanoplatforms as Calcium-Responsive Contrast Agents for Magnetic Resonance Imaging.
abstract: The preparation of ultrasmall and rigid platforms (USRPs) that are covalently coupled to macrocycle-based, calcium-responsive/smart contrast agents (SCAs), and the initial in vitro and in vivo validation of the resulting nanosized probes (SCA-USRPs) by means of magnetic resonance imaging (MRI) is reported. The synthetic procedure is robust, allowing preparation of the SCA-USRPs on a multigram scale. The resulting platforms display the desired MRI activity—i.e., longitudinal relaxivity increases almost twice at 7 T magnetic field strength upon saturation with Ca(2+). Cell viability is probed with the MTT assay using HEK-293 cells, which show good tolerance for lower contrast agent concentrations over longer periods of time. On intravenous administration of SCA-USRPs in living mice, MRI studies indicate their rapid accumulation in the renal pelvis and parenchyma. Importantly, the MRI signal increases in both kidney compartments when CaCl2 is also administrated. Laser-induced breakdown spectroscopy experiments confirm accumulation of SCA-USRPs in the renal cortex. To the best of our knowledge, these are the first studies which demonstrate calcium-sensitive MRI signal changes in vivo. Continuing contrast agent and MRI protocol optimizations should lead to wider application of these responsive probes and development of superior functional methods for monitoring calcium-dependent physiological and pathological processes in a dynamic manner.
authors.affiliation: Laboratoire MATEIS, INSA de Lyon, 69621, Villeurbanne Cedex, France.
authors.forename: Albert
authors.initials: A
authors.lastname: Moussaron
authors.affiliation: Department for Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, 72076, Tübingen, Germany.
authors.forename: Sandip
authors.initials: S
authors.lastname: Vibhute
authors.affiliation: CRMSB, UMR 5536, Université Bordeaux, 33076, Bordeaux, France.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bianchi
authors.affiliation: MR Neuroimaging Agents Group, Max Planck Institute for Biological Cybernetics, Spemannstr. 41, 72076, Tübingen, Germany.
authors.forename: Serhat
authors.initials: S
authors.lastname: Gündüz
authors.affiliation: Institut Lumière Matière, UMR CNRS 5306 - Université Lyon 1, 69622, Villeurbanne Cedex, France.
authors.forename: Shady
authors.initials: S
authors.lastname: Kotb
authors.affiliation: Institut Lumière Matière, UMR CNRS 5306 - Université Lyon 1, 69622, Villeurbanne Cedex, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Sancey
authors.affiliation: Institut Lumière Matière, UMR CNRS 5306 - Université Lyon 1, 69622, Villeurbanne Cedex, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Motto-Ros
authors.affiliation: CRMSB, UMR 5536, Université Bordeaux, 33076, Bordeaux, France.
authors.forename: Silvia
authors.initials: S
authors.lastname: Rizzitelli
authors.affiliation: CRMSB, UMR 5536, Université Bordeaux, 33076, Bordeaux, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Crémillieux
authors.affiliation: Institut Lumière Matière, UMR CNRS 5306 - Université Lyon 1, 69622, Villeurbanne Cedex, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Lux
authors.affiliation: Department for Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, 72076, Tübingen, Germany.|Department of Imaging Science and Biomedical Engineering, University of Manchester, Manchester, M13 9PT, UK.
authors.forename: Nikos K
authors.initials: NK
authors.lastname: Logothetis
authors.affiliation: Institut Lumière Matière, UMR CNRS 5306 - Université Lyon 1, 69622, Villeurbanne Cedex, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Tillement
authors.affiliation: MR Neuroimaging Agents Group, Max Planck Institute for Biological Cybernetics, Spemannstr. 41, 72076, Tübingen, Germany.
authors.forename: Goran
authors.initials: G
authors.lastname: Angelovski
mesh_terms: D000818:Animals; D002118:Calcium; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000737:chemistry*; D000067493:Dynamic Light Scattering; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007275:Injections, Intravenous; D007834:Lasers; D008024:Ligands; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D010316:Particle Size; D059629:Signal-To-Noise Ratio; D013057:Spectrum Analysis; D017186:Titrimetry; D018675:Toxicity Tests
chemical_list: D003287:Contrast Media; D008024:Ligands; D002118:Calcium
keywords: calcium; contrast agents; gadolinium; magnetic resonance imaging; nanoparticles