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Développement de nanovecteurs à base de nanoparticules d'or : Applications biomédicales

Abstract : The fight against cancer is a major challenge for public health, since cancer remains the leading cause of death in France. Conventional treatment like chemotherapy use very toxic products that induce large side effects. In this context, Gold nanoparticles (GNP) are of great interest thanks to their unique physical and chemical properties and are considered as promising agents for cancer therapy as drug delivery or photothermal agents. The aim of this thesis is to develop and study GNP and their interaction with biomolecules (proteins) in the framework of the cancer treatment. Firstly, two PEGyled GNP were synthetized and used as platform to develop nanovectors for doxorubicin ((DOX) anticancer drug), following two different strategies. The first strategy consists in synthesizing PEGyled GNP following “one-step” approach. Then the DOX loading on the nanoparticles was carried out by carbodiimide chemistry. The second strategy was performed by complexing DOX with gold ions, protected by PEG to form clusters. Afterwards these clusters are reduced to synthetize the GNP. The Physicochemical properties of these two kinds of GNP were characterised by TEM, optical absorption and Raman spectroscopy. Finally a cell viability study was carried out to compare the cytotoxicity effects of these two nanovectors on one pancreatic cancer cell line, PANC-1. In the second part, we studied the adsorption of three proteins of human blood serum (albumin, lysosime and glycoprotein) on citrate capped GNP. For this task, we have chosen to use scattering correlation spectroscopy as a tool to quantify the increase of the GNP hydrodynamic radius induced by the protein adsorption. The results showed that each protein has a specific orientation but also different binding affinity and cooperativity with the GNP surface. Finally, in the last part, we investigated the photothermal properties of citrate capped GNP of different sizes and shapes. The results show that the temperature rise depends on the plasmon resonance position compared to the excitation wavelength but also on the shape and the surface chemistry. This work was done to understand how photothermal effect produced by GNP can destroy cancer cells.
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Submitted on : Tuesday, March 31, 2020 - 8:07:11 PM
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Hanane Moustaoui. Développement de nanovecteurs à base de nanoparticules d'or : Applications biomédicales. Chimie thérapeutique. Université Sorbonne Paris Cité, 2018. Français. ⟨NNT : 2018USPCD065⟩. ⟨tel-02526969⟩

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