title: Long-term in vivo clearance of gadolinium-based AGuIX nanoparticles and their biocompatibility after systemic injection.
abstract: We previously reported the synthesis of gadolinium-based nanoparticles (NPs) denoted AGuIX (activation and guiding of irradiation by X-ray) NPs and demonstrated their potential as an MRI contrast agent and their efficacy as radiosensitizing particles during X-ray cancer treatment. Here we focus on the elimination kinetics of AGuIX NPs from the subcellular to whole-organ scale using original and complementary methods such as laser-induced breakdown spectroscopy (LIBS), intravital two-photon microscopy, inductively coupled plasma optical emission spectrometry (ICP-OES), transmission electron microscopy (TEM), and electrospray ionization mass spectrometry (ESI-MS). This combination of techniques allows the exact mechanism of AGuIX NPs elimination to be elucidated, including their retention in proximal tubules and their excretion as degraded or native NPs. Finally, we demonstrated that systemic AGuIX NP administration induced moderate and transient effects on renal function. These results provide useful and promising preclinical information concerning the safety of theranostic AGuIX NPs.
authors.affiliation: †Institut lumière matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon 69622 Villeurbanne cedex, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Sancey
authors.affiliation: †Institut lumière matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon 69622 Villeurbanne cedex, France.
authors.forename: Shady
authors.initials: S
authors.lastname: Kotb
authors.affiliation: †Institut lumière matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon 69622 Villeurbanne cedex, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Truillet
authors.affiliation: ‡GIN INSERM U836 UJF, Grenoble, 38706, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Appaix
authors.affiliation: †Institut lumière matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon 69622 Villeurbanne cedex, France.
authors.forename: Arthur
authors.initials: A
authors.lastname: Marais
authors.affiliation: †Institut lumière matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon 69622 Villeurbanne cedex, France.
authors.forename: Eloïse
authors.initials: E
authors.lastname: Thomas
authors.affiliation: ‡GIN INSERM U836 UJF, Grenoble, 38706, France.
authors.forename: Boudewijn
authors.initials: B
authors.lastname: van der Sanden
authors.affiliation: §LINA EA 4624-Laboratoire Interdisciplinaire d'étude des Nanoparticules Aérosolisées, Saint Etienne, 42023, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Klein
authors.affiliation: §LINA EA 4624-Laboratoire Interdisciplinaire d'étude des Nanoparticules Aérosolisées, Saint Etienne, 42023, France.
authors.forename: Blandine
authors.initials: B
authors.lastname: Laurent
authors.affiliation: §LINA EA 4624-Laboratoire Interdisciplinaire d'étude des Nanoparticules Aérosolisées, Saint Etienne, 42023, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Cottier
authors.affiliation: †Institut lumière matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon 69622 Villeurbanne cedex, France.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Antoine
authors.affiliation: †Institut lumière matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon 69622 Villeurbanne cedex, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Dugourd
authors.affiliation: †Institut lumière matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon 69622 Villeurbanne cedex, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Panczer
authors.affiliation: †Institut lumière matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon 69622 Villeurbanne cedex, France.
authors.forename: François
authors.initials: F
authors.lastname: Lux
authors.affiliation: ∥MATEIS, UMR 5510 INSA Lyon-CNRS, INSA Lyon, 69621 Villeurbanne, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Perriat
authors.affiliation: †Institut lumière matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon 69622 Villeurbanne cedex, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Motto-Ros
authors.affiliation: †Institut lumière matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon 69622 Villeurbanne cedex, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Tillement
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity; D001692:Biological Transport; D003287:Contrast Media / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity; D005682:Gadolinium / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity; D006801:Humans; D007267:Injections; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D053768:Metal Nanoparticles; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D012449:Safety; D014965:X-Rays
chemical_list: D001672:Biocompatible Materials; D003287:Contrast Media; D005682:Gadolinium
keywords: gadolinium; laser-induced breakdown spectroscopy; nanoparticle; renal function; theranostic; toxicity; two-photon microscopy