Synthèse de nanoparticules d'or fonctionnalisées par l'acide dihydrolipoïque : caractérisation, étude de stabilité et impact sur l'homéostasie redox cellulaire

Abstract : The aim of our work was to produce highly monodisperse and stable gold nanoparticles (AuNP) with potential for biomedical applications, and to evaluate the effect of AuNP surface properties on their uptake and cytotoxicity in a cultured cell line (rat-alveolar macrophages-NR8383). We synthesized AuNP either stabilized with citrate (Au-citratte) or capped with a dithiol, i.e. dihydrolipoic acid (Au@DHLA NP). The present study shows that the surface packing density is a crucial parameter to enhance the colloidal stability of AuNP in physiological conditions. We fully characterized the considered AuNP from a physico-chemical point of view. Indeed, we optimized a spectrocolorimetric and a HPLC method to evaluate the properties of AuNP. We studied the biological effects of AuNP. Under cell-free conditions, our results reveal that AuNP coating affects their reactivity with biomolecules, i.e. reduced glutathione (GSH), S-nitrosoglutathione and bovine serum albumin (Au-citrate interact with all molecules), the cellular uptake (Au-citrate are two times more effective) and redox status (Au-citrate decrease the intracellular GSH level by ca 20%) with no apparent relationship with ROS formation. Furthermore, both AuNP appear not to induce mRNA expression related to inflammatory response (tnfa), oxidative stress (ncf1) and apoptosis (nfkb2), parameters of main importance to preserve cellular integrity and body safety, and to assure pharmaceutical platform function
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Juliana Tournebize-Pego Lima. Synthèse de nanoparticules d'or fonctionnalisées par l'acide dihydrolipoïque : caractérisation, étude de stabilité et impact sur l'homéostasie redox cellulaire. Médecine humaine et pathologie. Université de Lorraine, 2012. Français. ⟨NNT : 2012LORR0030⟩. ⟨tel-01749197⟩

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