title: Massive Intracellular Biodegradation of Iron Oxide Nanoparticles Evidenced Magnetically at Single-Endosome and Tissue Levels.
abstract: Quantitative studies of the long-term fate of iron oxide nanoparticles inside cells, a prerequisite for regenerative medicine applications, are hampered by the lack of suitable biological tissue models and analytical methods. Here, we propose stem-cell spheroids as a tissue model to track intracellular magnetic nanoparticle transformations during long-term tissue maturation. We show that global spheroid magnetism can serve as a fingerprint of the degradation process, and we evidence a near-complete nanoparticle degradation over a month of tissue maturation, as confirmed by electron microscopy. Remarkably, the same massive degradation was measured at the endosome level by single-endosome nanomagnetophoretic tracking in cell-free endosomal extract. Interestingly, this spectacular nanoparticle breakdown barely affected iron homeostasis: only the genes coding for ferritin light chain (iron loading) and ferroportin (iron export) were up-regulated 2-fold by the degradation process. Besides, the magnetic and tissular tools developed here allow screening of the biostability of magnetic nanomaterials, as demonstrated with iron oxide nanocubes and nanodimers. Hence, stem-cell spheroids and purified endosomes are suitable models needed to monitor nanoparticle degradation in conjunction with magnetic, chemical, and biological characterizations at the cellular scale, quantitatively, in the long term, in situ, and in real time.
authors.affiliation: Laboratoire Matière et Systèmes Complexes (MSC), UMR 7057, CNRS and Université Paris Diderot , 75205 Cedex 05 Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Mazuel
authors.affiliation: Laboratoire Matière et Systèmes Complexes (MSC), UMR 7057, CNRS and Université Paris Diderot , 75205 Cedex 05 Paris, France.
authors.forename: Ana
authors.initials: A
authors.lastname: Espinosa
authors.affiliation: Laboratoire Matière et Systèmes Complexes (MSC), UMR 7057, CNRS and Université Paris Diderot , 75205 Cedex 05 Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Luciani
authors.affiliation: Laboratoire Matière et Systèmes Complexes (MSC), UMR 7057, CNRS and Université Paris Diderot , 75205 Cedex 05 Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Reffay
authors.affiliation: ImagoSeine, Electron Microscopy Facility, Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot , Sorbonne Paris Cité, 75205 Cedex 13 Paris, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Le Borgne
authors.affiliation: Inserm, U1148, Laboratory for Vascular Translational Science, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, F-93017 Bobigny, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Motte
authors.affiliation: LISA, CNRS UMR 7583, Université Paris-Diderot and Université Paris-Est Créteil, 94400 Créteil, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Desboeufs
authors.affiliation: Sorbonne Universités, Physicochimie des Electrolytes et Nanosystèmes InterfaciauX (PHENIX), UMR 8234, Université Pierre et Marie Curie UPMC-CNRS, 75252 Cedex 05 Paris, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Michel
authors.affiliation: Istituto Italiano di Tecnologia , I-16163 Genoa, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Pellegrino
authors.affiliation: Inserm, U1148, Laboratory for Vascular Translational Science, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, F-93017 Bobigny, France.|Service de Médecine Nucléaire, Hôpital Avicenne Assistance Publique-Hôpitaux de Paris, F-93009 Bobigny, France.
authors.forename: Yoann
authors.initials: Y
authors.lastname: Lalatonne
authors.affiliation: Laboratoire Matière et Systèmes Complexes (MSC), UMR 7057, CNRS and Université Paris Diderot , 75205 Cedex 05 Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Wilhelm
mesh_terms: D011992:Endosomes; D005290:Ferric Compounds; D008280:Magnetics; D058185:Magnetite Nanoparticles; D008962:Models, Theoretical; D053758:Nanoparticles; D018874:Spheroids, Cellular
chemical_list: D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide
keywords: biodegradation; endosomes; iron metabolism; iron oxide nanoparticles; nanomagnetism; spheroids; stem cells