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Traitement photodynamique interstitiel vasculaire stéréotaxique des tumeurs cérébrales guidé par imagerie : intérêt des nanoparticules multifonctionnelles ciblant neuropiline-1

Abstract : Photodynamic therapy (PDT) for brain tumors appears to be complementary to conventional treatments. Number studies show the major role of the vascular effect in the tumor eradication by PDT. To promote this vascular effect, a selective targeting of neuropilin-1 (NRP-1), mainly over-expressed by tumor angiogenic vessels, was investigated using a photosensitizer coupled to a ligand peptide. We validated the interest of using this active-targeting strategy to promote this vascular effect by the induction of tissue factor expression immediately post-PDT. For interstitial PDT (iPDT) of brain tumors guided by real-time imaging, multifunctional nanoparticles consisting of a surface-localized tumor vasculature targeting NRP-1 and encapsulated PDT and imaging agents, have been developed. The selected nanoparticles are favourable to a photosensitizer targeting strategy for iPDT combined with MRI. Characterization studies of the nanoparticles reveal a photodynamic efficiency and demonstrate a molecular affinity of the functionalized nanoparticle to NRP-1 target. After intravenous injection of the multifunctional nanoparticles into rats with intracranial glioma, we demonstrate a positive contrast enhancement of the tumor tissue by MRI, allowing the optimization of the optical fiber implantation. Perfusion MRI data and NRP-1 protein expression of the tumor and brain adjacent to tumor tissues check selectivity of the functionalized nanoparticle. The combination of non-invasive techniques of imaging (MRI, MRS, PET/CT) validates this concept of iPDT guided by MRI
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http://docnum.univ-lorraine.fr/prive/SCD_T_2011_0119_BECHET.pdf
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https://hal.univ-lorraine.fr/tel-01746272
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Submitted on : Thursday, March 29, 2018 - 10:29:44 AM
Last modification on : Friday, March 6, 2020 - 9:45:07 AM

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Denise Bechet. Traitement photodynamique interstitiel vasculaire stéréotaxique des tumeurs cérébrales guidé par imagerie : intérêt des nanoparticules multifonctionnelles ciblant neuropiline-1. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2011. Français. ⟨NNT : 2011NAN10119⟩. ⟨tel-01746272⟩

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