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Nouvelle approche en thérapie anti-tumorale : développement de nanovecteurs du calcitriol ciblant les macrophages

Abstract : Tumor associated macrophages (Mɸ) orchestrate the different stages of tumor development. They are able to internalize nanoparticles (NPs) and are known for their phenotypic plasticity, which make them interesting targets for cancer treatment through the storage of NPs or a modulation of their activity towards the neoplastic cells. Calcitriol, the active metabolite of vitamin D, exerts both anticancer and immunomodulatory activities. Its vectorization via NPs is an interesting therapeutic approach to potentiate its activities while limiting its side effects, which hamper its current clinical use in chemotherapy. We developed poly (D, L) lactic acid and triglyceride-based NPs (1:2 ratio) measuring 200 nm and exhibiting a sustained release of calcitriol. In vitro studies, performed on breast cancer cells (MCF-7), showed the advantages of a sustained release of calcitriol regarding its antiproliferative activity with a 65%-decrease in cell viability after 10 days compared to unexposed cells, while it was unobservable for free calcitriol. The implication of Mɸ in the cytotoxic activity of calcitriol towards MCF-7 cells and MV4-11 cells (leukemia) cells has been demonstrated using an in vitro co-culture model. Calcitriol-NPs showed a sustained cytotoxic activity towards MCF-7 cells in co-cultures after 10 days, through their uptake by Mɸ, with a decrease in cell viability of 80% vs 30% in mono-cultures
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https://tel.archives-ouvertes.fr/tel-03018105
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Submitted on : Sunday, November 22, 2020 - 1:06:22 AM
Last modification on : Sunday, November 22, 2020 - 3:24:47 AM

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Sabrina Nicolas. Nouvelle approche en thérapie anti-tumorale : développement de nanovecteurs du calcitriol ciblant les macrophages. Ingénierie biomédicale. Université de Lyon, 2018. Français. ⟨NNT : 2018LYSE1248⟩. ⟨tel-03018105⟩

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