title: In situ quantification of diverse titanium dioxide nanoparticles unveils selective endoplasmic reticulum stress-dependent toxicity.
abstract: Although titanium dioxide nanoparticles (TiO2NPs) have been extensively studied, their possible impact on health due to their specific properties supported by their size and geometry, remains to be fully characterized to support risk assessment. To further document NPs biological effects, we investigated the impact of TiO2NPs morphology on biological outcomes. To this end, TiO2NPs were synthesized as nanoneedles (NNs), titanate scrolled nanosheets (TNs), gel-sol-based isotropic nanoparticles (INPs) and tested for perturbation of cellular homeostasis (cellular ion content, cell proliferation, stress pathways) in three cell types and compared to the P25. We showed that TiO2NPs were internalized at various degrees and their toxicity depended on both titanium content and NPs shape, which impacted on intracellular calcium homeostasis thereby leading to endoplasmic reticulum stress. Finally, we showed that a minimal intracellular content of TiO2NPs was mandatory to induce toxicity enlightening once more the crucial notion of internalized dose threshold beside the well-recognized dose of exposure.
authors.affiliation: a Centre d'Etudes Nucléaires Bordeaux Gradignan (CENBG), Université de Bordeaux , Gradignan , France.|b CNRS, UMR5797, Centre d'Etudes Nucléaires Bordeaux Gradignan (CENBG) , Gradignan , France.
authors.forename: Marina
authors.initials: M
authors.lastname: Simon
authors.affiliation: a Centre d'Etudes Nucléaires Bordeaux Gradignan (CENBG), Université de Bordeaux , Gradignan , France.|b CNRS, UMR5797, Centre d'Etudes Nucléaires Bordeaux Gradignan (CENBG) , Gradignan , France.
authors.forename: Gladys
authors.initials: G
authors.lastname: Saez
authors.affiliation: a Centre d'Etudes Nucléaires Bordeaux Gradignan (CENBG), Université de Bordeaux , Gradignan , France.|b CNRS, UMR5797, Centre d'Etudes Nucléaires Bordeaux Gradignan (CENBG) , Gradignan , France.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Muggiolu
authors.affiliation: c CNRS, UPR9048, Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB) , Pessac , France.|d Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), Université de Bordeaux , Pessac , France.
authors.forename: Magali
authors.initials: M
authors.lastname: Lavenas
authors.affiliation: a Centre d'Etudes Nucléaires Bordeaux Gradignan (CENBG), Université de Bordeaux , Gradignan , France.|b CNRS, UMR5797, Centre d'Etudes Nucléaires Bordeaux Gradignan (CENBG) , Gradignan , France.|c CNRS, UPR9048, Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB) , Pessac , France.|d Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), Université de Bordeaux , Pessac , France.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Le Trequesser
authors.affiliation: a Centre d'Etudes Nucléaires Bordeaux Gradignan (CENBG), Université de Bordeaux , Gradignan , France.|b CNRS, UMR5797, Centre d'Etudes Nucléaires Bordeaux Gradignan (CENBG) , Gradignan , France.
authors.forename: Claire
authors.initials: C
authors.lastname: Michelet
authors.affiliation: a Centre d'Etudes Nucléaires Bordeaux Gradignan (CENBG), Université de Bordeaux , Gradignan , France.|b CNRS, UMR5797, Centre d'Etudes Nucléaires Bordeaux Gradignan (CENBG) , Gradignan , France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Devès
authors.affiliation: a Centre d'Etudes Nucléaires Bordeaux Gradignan (CENBG), Université de Bordeaux , Gradignan , France.|b CNRS, UMR5797, Centre d'Etudes Nucléaires Bordeaux Gradignan (CENBG) , Gradignan , France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Barberet
authors.affiliation: e INSERM, ERL440, "Oncogenesis Stress Signaling", Université Rennes 1 , Rennes , France.|f Centre de Lutte Contre le Cancer Eugène Marquis , Rennes , France.
authors.forename: Eric
authors.initials: E
authors.lastname: Chevet
authors.affiliation: g INSERM, U869, IECB, Laboratoire ARNA , Bordeaux , France.|h Université de Bordeaux, U869, IECB, Laboratoire ARNA , Bordeaux , France.
authors.forename: Denis
authors.initials: D
authors.lastname: Dupuy
authors.affiliation: c CNRS, UPR9048, Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB) , Pessac , France.|d Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), Université de Bordeaux , Pessac , France.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Delville
authors.affiliation: a Centre d'Etudes Nucléaires Bordeaux Gradignan (CENBG), Université de Bordeaux , Gradignan , France.|b CNRS, UMR5797, Centre d'Etudes Nucléaires Bordeaux Gradignan (CENBG) , Gradignan , France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Seznec
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000235:genetics; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D015603:Keratinocytes; D053758:Nanoparticles / Q000032:analysis* / Q000633:toxicity*; D010316:Particle Size; D060888:Real-Time Polymerase Chain Reaction; D013499:Surface Properties; D014025:Titanium / Q000032:analysis* / Q000633:toxicity*; D059467:Transcriptome / Q000187:drug effects
chemical_list: C009495:titanium dioxide; D014025:Titanium
keywords: ER stress; Titanium dioxide nanoparticles; calcium homeostasis; in situ quantification; morphology-dependant toxicology