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Master Thesis

Nanoparticules de numéro atomique élevé en onco-radiothérapie : état des lieux, et évaluation de leur potentiel radio-potentialisant

Abstract : Objectifs: to define place and impact of nanoparticles in radio-oncology. To study high Z nanoparticles radiopotentialization with a literature review and experimentation by Titane Dioxyde nanoparticles (TiO2NPs). Materials and Methods: IB115 cell line (liposarcoma) were exposed to TiO2Nps, at 0.2 et 4 µg.cm-2, and were irradiated at doses of 0, 1, 2 and 6 Gy by 6MeV photons on a medical LINAC facility. Multi-elementay chemical composition were analysed by AIFAIRA facility after cryofixation. Stress pathways genes induction (NFKB, NRF2, p53, ATF4, ATF6, ERSE) were analysed by BMYScreen facility. Mitochondrial function and apoptosis were analysed by immunodetection (Cytochrome C, clived Caspase 3). Endoplasmic Reticulum (ER) and oxidative stress pathways were analysed by RTqPCR. Results: TiO2NPs internalization is exclusively intracytoplasmic and perinuclear. It induce a Cytochrome C cytoplasmic relocalization and a Clived Caspase 3 activation by a mitochondrial action. TiO2Nps induce an activation of ER stress pathway and an intracellular Calcium (CAic) increase, without oxidative stress. Ionizing radiation exposition leads to a CAic increase and a ER stress pathway activation. NPs-radiotherapy combination potentialize the CAic increase and ER stress pathway activation. Conclusions: TiO2NPs are not biologically inert. Combined with radiotherapy, they imply the ER stress pathway, a mitochondrial dysfunction, an intrinsic apoptotic pathway activation and a calcic homeostasis alteration. This combination’s mode of action is therefor a radiosensibilization, and not only a radiopotentialization.
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https://dumas.ccsd.cnrs.fr/dumas-02414343
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Florent Vilotte. Nanoparticules de numéro atomique élevé en onco-radiothérapie : état des lieux, et évaluation de leur potentiel radio-potentialisant. Sciences du Vivant [q-bio]. 2019. ⟨dumas-02414343⟩

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