WorldCat Identities

Le Guevel, Xavier (1978-....).

Works: 3 works in 4 publications in 1 language and 5 library holdings
Roles: Author, Thesis advisor, Opponent, Other
Publication Timeline
Most widely held works by Xavier Le Guevel
Applications des nanoclusters de métaux nobles pour lediagnostic et la thérapie ciblée du cancer by Estelle Porret( )

1 edition published in 2019 in French and held by 2 WorldCat member libraries worldwide

Gold nanoparticles (Au NPs) have shown promising results in nanomedicine applied to oncology. They are capable of accumulating in tumor areas, inducing a therapeutic effect by delivering drugs or a photo-/radiotherapeutic effect thanks to their energy absorption properties. They also allow diagnosis by different imaging techniques. This dual activity defines them as theranostic agents. Gold nanoclusters (Au NCs) define an interesting sub-family of Au NPs. They are composed of about ten to hundred gold atoms stabilized by organic molecules. Their size smaller than ~8 nm allows them to be eliminated by the kidneys and to exhibit photoluminescence (PL) properties until infrared wavelengths, which are suitable for in vivo optical imaging. They can also induce cell death under irradiation due to the intrinsic properties of gold. Their optical features, pharmaco-kinetic and tumor accumulation are highly sensitive to size and surface chemistry modification. Currently, preclinical results are not sufficient for clinical transfer and it is necessary to improve the characterization of Au NCs and to study their behaviour in vitro and in vivo.In this context, my thesis project focused on the functionalization of Au NCs in order to improve their accumulation in tumors. The first strategy is based on the self-aggregation of Au NCs in the tumor microenvironment. For this purpose, the surface of the Au NCs was either functionalized with i) molecules promoting bioorthogonal click chemistry reactions, or ii) complementary oligonucleotides that can hybridize. The self-aggregation of Au NCs in solution confirmed the increase in PL by inter-particle energy transfer. The self-agregation of Au NCs could potentially improve the therapeutic effect, but the Au NCs still need to be characterized in vivo. The second strategy consisted in increasing the affinity of Au NCs for cells by adding controlled amounts of arginine on their surface. Indeed, arginine is known to promote electrostatic interaction with plasma membranes and cellular internalization. We have determined the maximum arginine threshold per Au NCs, allowing to increase the PL while keeping their small size with high colloidal stability. The best candidates have a high capacity for electrostatic interaction with artificial membranes even in the presence of serum, suggesting that the opsonization of Au NCs is low. Their interaction (< 5min) and internalization (<30 min) capacities are rapid, and have been confirmed on human melanoma cells in vitro, without significant toxicity. However, according to a study on irradiated spheroids performed in our team, the addition of arginines would have a "trapping" effect on the production of reactive oxygen species, reducing the radiosensitizing power of Au NCs. The presence of positive charges on Au NCs containing arginines and their internalization capacity also can serve in vitro to deliver anionic polymers and biomolecules such as siRNA. However, these Au NCs administered intravenously to tumor-bearing mice are eliminated extremely rapidly by the kidneys, thus reducing their ability to accumulate in tumors. This work showed that the functionalization of Au NCs strongly influences their optical and physicochemical properties, their interactions with cells and their theranostic effects. It would be interesting to apply these strategies to Au NCs circulating longer in the blood to demonstrate the effect of these functionalizations on tumor diagnostics and therapy
Elaboration de sols de silice colloïdale en milieu aqueux : fonctionnalisation, propriétés optiques et de détection chimique des revêtements correspondants by Xavier Le Guevel( Book )

2 editions published in 2006 in French and held by 2 WorldCat member libraries worldwide

L'objectif de ce travail était d'étudier la réactivité de surface de nanoparticules de silice au travers des propriétés physico-chimiques du matériau élaboré sous forme de suspensions colloïdales ou de couches minces. Les applications sont multiples et elles sont illustrées dans ce travail par la réalisation de revêtements optiques pour des composants lasers ainsi que dans la mise au point de capteurs chimiques pour la détection de composés nitroaromatiques
Biotransformations, dégradation et cycle de vie des nanoparticules d'or en milieu intracellulaire by Alice Balfourier( )

1 edition published in 2019 in French and held by 1 WorldCat member library worldwide

Gold nanoparticles display unique optical properties, and are considered as promising devices for medical imaging, therapy and diagnostic. Nevertheless, nanoparticles life cycle is still poorly understood at the cellular range. On the short term, nanoparticles are internalized by cells and sequestrated into the lysosomes, which are the intracellular vesicles responsible for the degradation and recycling of damaged endogenous and exogenous compounds. We focus our study on this step of nanoparticle life cycle, and more precisely on the lysosome and its nanoparticles content. Firstly, we studied this system from the lysosome point of view, and the impact of gold nanoparticles on its structural and functional integrity. Secondly, we considered the nanoparticles point of view, and the biotransformation they undergo in the lysosome. Once sequestrated into the lysosome, nanoparticles aggregate which modulate their optical properties, and thus modify their therapeutic potential. In order to capture this first biotransformation, we characterized the nature of these intracellular aggregates, and highlight the therapeutic potential of gold nanosphere aggregates, while they are considered as medically irrelevant when dispersed. Finally, we focus our study on the fate of gold nanoparticles in cells during six months. We demonstrate that gold nanoparticles were degraded in vitro, despite the current dogma that assert that gold nanoparticles are bio-inert. This process was proven to take place within days, and to be followed by the recrystallization of released gold. Transcriptomics analysis of the biological pathways activated in this biodegradation reveals the biological actors involved in this transformation, and to identify similarities between the response to gold nanoparticles and ionic gold, suggesting a common gold metabolism. This analogy opens up new prospects for the understanding of gold nanoparticle life cycle, but also for therapy. To conclude, the work presented in this thesis put into light new steps in gold nanoparticles life cycle, that enable us to propose therapeutic strategy that take advantages from fortuitous phenomena, while keeping in mind nanotoxicological issues
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Audience level: 0.95 (from 0.91 for Elaboratio ... to 0.99 for Elaboratio ...)

French (4)