In situ quantification of diverse titanium dioxide nanoparticles unveils selective endoplasmic reticulum stress-dependent toxicity

Marina Simon (1) , Gladys Saez (1) , Giovanna Muggiolu (1) , Magali Lavenas (2) , Quentin Le Trequesser (1, 2) , Claire Michelet (1) , Guillaume Devès (1) , Philippe Barberet (1) , Eric Chevet (3, 4) , Denis Dupuy (5) , Marie-Hélène Delville (2) , Hervé Seznec (1)

1 CENBG - Centre d'Etudes Nucléaires de Bordeaux Gradignan
2 ICMCB - Institut de Chimie de la Matière Condensée de Bordeaux
3 CRLCC - CRLCC Eugène Marquis
4 COSS - Chemistry, Oncogenesis, Stress and Signaling
5 ARNA - Régulations Naturelles et Artificielles

Although titanium dioxide nanoparticles (TiO2 NPs) 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 TiO2 NPs morphology on biological outcomes. To this end, TiO2 NPs 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 TiO2 NPs 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 TiO2 NPs was mandatory to induce toxicity enlightening once more the crucial notion of internalized dose threshold beside the well-recognized dose of exposure.

Mots clés: ER stress; morphology-dependant toxicology; Titanium dioxide nanoparticles; calcium homeostasis; in situ quantification

Domaines: Toxicologie; Cancer

Marina Simon, Gladys Saez, Giovanna Muggiolu, Magali Lavenas, Quentin Le Trequesser, et al.. In situ quantification of diverse titanium dioxide nanoparticles unveils selective endoplasmic reticulum stress-dependent toxicity. Nanotoxicology, 2017, 11 (1), pp.134-145. ⟨10.1080/17435390.2017.1278803⟩. ⟨hal-01447226⟩