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Développement de nanoparticules polymères pour le ciblage des macrophages et la modulation des leurs fonctions physiologiques

Abstract : Macrophages are the major leukocyte population present in tumors, so-called tumor-associated macrophages (TAM), promoting tumor growth. These macrophages could be an interesting therapeutic target for nanoparticulate delivery systems known to be easily recognized and phagocytosed by macrophages after local or parenteral administration. The aim of this work was to develop polymeric nanoparticles (NP) for targeting TAM. NP could modulate macrophage functions or use them as storage of anticancer drugs. After a formulation study, the 200 nm NP of poly(D, L) lactic acid were selected. These NP showed a good internalization by macrophages in vitro and specific targeting of TAM in human glioma tumor implanted in nude mice after intratumoral injection of NP. All-trans retinoic acid (RA, immuno-modulator) was first encapsulated with an encapsulation efficiency of 90%. RA-NP have a sustained release profile for 4 days and enhance stability of the RA. Changes in gene expression of RA-NP treated macrophages were observed in vitro. Secondly, active-metabolites of vitamin D3 (25-OH-vitamin D3 and 1,25-(OH)2-vitamin D3) were encapsulated for their anticancer properties. The aim was to target the tumor cells via TAM avoiding the hypercalcemia produced by high doses of vitamin D3. In vitro evaluations on breast cancer cell line (MCF-7) highlighted NP advantages to extend and enhance the antiproliferative action of vitamin D3 derivatives
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Submitted on : Wednesday, February 12, 2014 - 10:19:07 AM
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Eyad Almouazen. Développement de nanoparticules polymères pour le ciblage des macrophages et la modulation des leurs fonctions physiologiques. Médecine humaine et pathologie. Université Claude Bernard - Lyon I, 2013. Français. ⟨NNT : 2013LYO10121⟩. ⟨tel-00945306⟩

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