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Synthesis of Biocompatible Nanoparticulate Coordination Polymers for Diagnostic and Therapeutic ApplicationsKandanapitiye, Murthi S. 27 April 2015 (has links)
No description available.
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Single-cell tracking of therapeutic cells using Laser Ablation-Inductively Coupled Plasma-Mass SpectrometryManagh, Amy J. January 2014 (has links)
Cellular therapy is emerging as a clinically viable strategy in the field of solid organ transplantation, where it is expected to reduce the dependency on conventional immunosuppression. This has produced a demand for highly sensitive methods to monitor the persistence and tissue distribution of administered cells in vivo. However, tracking cells presents significant challenges. In many cases transplanted cells are autologous with the immune system of the transplant recipient, and hence are invisible to typical methods of detection. To enable their differentiation, the cells must be labelled with a suitable, non-toxic and long lifetime label, prior to their administration to patients. In addition, administered cells represent only a small fraction of the recipient's endogenous cells, which necessitates the use of an extremely sensitive detection method. Laser ablation – inductively coupled plasma – mass spectrometry (LA-ICP-MS) is an exquisitely sensitive analytical technique, capable of imaging trace elements in complex samples, at high spatial resolution.
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Synthèse et caractérisation de nanomatériaux hybrides innovants pour le biomédical / Synthesis and characterization of new hybrids nanomaterials for biomedical applicationsVenturini, Pierre 15 December 2017 (has links)
Depuis quelques décennies, les nanomatériaux et tout particulièrement les nanoparticules d’oxyde de fer (magnétite/maghémite) superparamagnétiques ont connus un intérêt croissant en nano-médecine. Leur biocompatibilité et leurs propriétés magnétiques permettent notamment leur utilisation à des fins de diagnostic (IRM, Imagerie optique et nucléaire…) et de thérapie (Hyperthermie, nano vectorisation…). Au cours de cette thèse, la première étape a consisté à étudier en détails l’influence de plusieurs paramètres de synthèse sur les propriétés finales des nanoparticules d’oxyde de fer magnétique. Cette étude avait pour but de développer et d’optimiser une méthode de synthèse dérivée de la méthode de synthèse classique dite de co-précipitation mais modifiée par ajout de ligand citrates au cours de la synthèse. Des nanoparticules d’oxyde de fer d’une taille pouvant être contrôlée entre 4 et 13 nm recouvertes par une couronne de ligands citrates ont ainsi été synthétisées, celles-ci présentent une aimantation à saturation atteignant jusqu’à 75 emu/g d’oxyde de fer qui est une valeur particulièrement haute pour des nanoparticules de cette taille. Tout au long de ce travail, la caractérisation de ces nanoparticules par un panel étendu de techniques (MET, DRX, Mössbauer, IRTF, XPS, mesures magnétiques, DLS …) à permis notamment d’étudier de façon précise les relations existantes entre la taille, le taux de ligand, la composition et les propriétés magnétiques des nanoparticules synthétisées. Ces nanoparticules fonctionnalisées par des citrates ont ensuite été testées en milieu biologique afin d’évaluer leur internalisation dans les cellules et leur cytotoxicité. Dans un deuxième temps, d’autres travaux ont été menés sur les nanoparticules d’oxyde de fer. Notamment le remplacement des ligands citrates par un polymère bio-inspiré pouvant, selon les fonctions chimiques qui lui sont adjointes, avoir de multiples applications dans le domaine biomédical / From decades now, nanomaterials and especially superparamagnetic iron oxide nanoparticles are studied for their numerous applications in nanomedecine area. The biocompatibility and the magnetic properties of such nano-objects allow their utilization for diagnostic (MRI, optical imagery, PET…) and for therapy application (nanovectorization, hyperthermia…) During this thesis work, the first step was to study the influence of several synthesis parameters on the final properties of the magnetic iron oxide nanoparticles. The aim of this study was the development and the optimization of the widely used way of synthesis by co-precipitation modified by a ligand addition during the growth step of the synthesis. Citrate capped iron oxide nanoparticles with a controlled size between 4 and 13 nm have been synthesized, the saturation magnetization of these nanoparticles reach 75 emu/g of iron oxide, this value is particularly high for nanoparticles of such sizes. During this work, the large panel of characterizations performed on these nanoparticles (TEM, XRD, Mössbauer, FTIR, XPS, DLS, Magnetic measurement) allowed to study precisely the relations between size, ligand ratio, composition and magnetic properties of the synthesized nanoparticles. The interaction between the synthesized citrate capped nanoparticles and biological materials such as human cells have been investigated in-vitro notably to evaluate cells internalization and citotoxicity. In a second step, some additional works have been performed on the citrate capped iron oxide nanoparticles in order to replace the citrate ligand by a bio-inspired polymer (poly-oxazoline). This polymer can have multiple biomedical applications depending of the pendent chemical groups that have been fixed on it
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Magnetic polyion complex micelles as therapy and diagnostic agents / Micelles polymères magnétiques comme agents pour la thérapie et l'imagerieNguyen, Vo Thu An 16 September 2015 (has links)
Ce manuscrit de thèse présente la synthèse de nanoparticules d’oxyde de fer superparamagnétiques couramment appelées SPIONs servant d’agents de contraste pour l’imagerie par résonance magnétique (IRM) et la génération de chaleur pour la thérapie cellulaire par hyperthermie induite par champ magnétique radiofréquence (HMRF). Le contrôle des tailles et de la distribution en tailles des SPIONs et donc de leurs propriétés magnétiques a été obtenu en utilisant un copolymère arborescent G1 (substrat de polystyrène branché en peigne noté G0, greffé avec des groupements pendants poly(2-vinyle pyridine) ) comme milieu « gabarit », tandis que la stabilité colloïdale et la biocompatibilité des SPIONs ont été apportées par un procédé de poly-complexation ionique grâce à un copolymère double-hydrophile acide polyacrylique-bloc-poly(acrylate de 2-hydroxyéthyle) PAA-b-PHEA. / This Ph.D. dissertation describes the synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) designed to serve as magnetic resonance imaging (MRI) contrast agents and for heat generation in cellular radiofrequency magnetic field hyperthermia (MFH) treatment. Control over the size and size distribution of the iron oxide nanoparticles (NPs), and thus over their magnetic properties, was achieved using a G1 arborescent copolymer (comb-branched (G0) polystyrene substrate grafted with poly(2-vinylpyridine) side chains, or G0PS-g-P2VP) as a template. Good colloidal stability and biocompatibility of the SPIONs were achieved via the formation of polyion complex (PIC) micelles with a poly(acrylic acid)-block-poly(2-hydroxyethyl acrylate) (PAA-b-PHEA) double-hydrophilic block copolymer.
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Nanoparticules multifonctionelles pour la résonance magnétique et l'imagerie fluorescente / Multifunctional nanoparticles for MR and fluorescence imagingPinho, Sonia Luzia Claro 14 December 2011 (has links)
Cette thèse décrit une stratégie de synthèse de nouvelles générations des nanoparticules (NPs) pour applications biomédicales, visant à une amélioration de leurs performances pour l’imagerie, le diagnostic thérapeutique. Ces NPs présentent plusieurs fonctionnalités leur permettant de réaliser des tâches multiples. Deux types de sondes bimodales ont été développés et étudiés afin d'évaluer leur potentiel comme agents (1) de contraste en IRM et (2) luminescents. Ces objetscombinent les propriétés des complexes de lanthanide (Ln3+) et celles des NPs de silice ou de type coeur-écorce Fe2O3@SiO2 pour une imagerie bimodale. Ces NPs testées sur des cellules vivantes ont permis d’illustrer la preuve du concept aussi bien en IRM avec une augmentation d'intensité des images et un impact significatif sur les relaxivities r1, r2 et r2* qu’en photoluminescence. L’étude du système coeur-écorce a montré que l’influence du contrôle fin de l’écorce autour du noyau d'oxyde de fer a pu être modélisée. / This thesis describes a strategy of synthesis of new generations of nanoparticles (NPs) for biomedical applications, aiming at an improvement of their performances for the imaging, and the therapeutic diagnosis. These NPs present several functionalities enabling them to carry out multiple tasks. Two types of bimodal probes were developed and studied so as to evaluate their potential as contrast agents (1) in MRI and (2) and luminescence. These objects combine the properties of the lanthanide complexes (Ln3+) and those of NPs of silica or core/shell Fe2O3@SiO2 for a bimodal imaging. These NPs tested on living cells were able to illustrate the proof of the concept not only in MRI with an increase of intensity of the images and a significant impact on the relaxivities r1, r 2 and r2* but also in photoluminescence. The study of the core/shell system showed that the influence of the fine control of the shell around the iron oxide core could be modeled.
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Estudos conformacionais em compostos contendo íons lantanídeosOliveira, Maria Weruska Pereira de 13 November 2008 (has links)
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Previous issue date: 2008-11-13 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Lanthanide macrocyclic complexes, especially containing Gd(III)
ions, are largely used as contrast agents in the medical diagnostic
technique named Magnetic Resonance Imaging (MRI). Theoretical
investigation of these compounds by molecular modeling methods is an
emerging research area today.
In this work we have performed a conformational study of the
following supramolecular compounds: the macrocyclic ligands 1,4,7,10-
tetraazacyclododecane (DOTA) and 1,4,7,10-tetraazacyclododecane-
1,4,7,10-tetraacetic acid (H4DOTA) and the macrocyclic complexes
[Gd(DOTA).H2O]- and Gd(PhenHDO3A).H2O, where PhenHDO3A is (rel-10-
[(5R,6R)-5,6-dihydro-6-hydroxy-1,10-Phenanthroline-5-yl)-1,4,7,10-
tetraazacyclododecane-1,4,7-triacetic acid).
For this, we have developed and carried out a procedure that
involves: (1) the sampling of the conformation space of these compounds
through some short molecular dynamics at different temperatures and (2)
full geometry optimization in the geometries obtained in the previous
stage using semi-empirical AM1 method for the macrocyclic ligands and
Sparkle/AM1 model for the macrocyclic lanthanide complexes.
Our results revealed that the high flexibility of non-coordinated
macrocyclic ligands DOTA and H4DOTA, helped us to test the ability of our
methodology to sample different regions of conformation space of these
compounds.
For the [Gd(DOTA).H2O]- complex, we were capable to find the
same conformational isomers which were reported in published works as
well as to comprehend relevant details about the mobility of the
coordinated water molecule. Furthermore, we also were capable to
identify some intermediate local minima related to the dynamics of
rotation of the coordinated acetate groups in the studied complexes as
well as to the dynamics of ring inversion of the coordinated
tetraazadodecane moiety in the Gd(PhenHDO3A).H2O.
In conclusion, we possess now an interesting strategy to conduct the
search for conformational isomers of these compounds. This knowledge is
very important to be applied in the rational design of new molecules to act
as contrast agent in MRI. / Complexos macrocíclicos de lantanídeos, em especial com o íon
Gd(III), são cada vez mais utilizados como agentes de contrastes na
técnica médica de diagnóstico, imagem por ressonância magnética nuclear
(MRI). O estudo teórico de novos agentes de contrastes através de
modelagem molecular é uma área de pesquisa em grande expansão.
No nosso trabalho fizemos um estudo conformacional dos seguintes
compostos supramoleculares: os ligantes macrocíclicos 1,4,7,10-
tetraazaciclododecano (DOTA) e ácido 1,4,7,10-tetraazaciclododecano-
1,4,7,10-tetraacético (H4DOTA), o complexo macrocíclico
[Gd(DOTA)H2O]- e o complexo macrocíclico Gd(PhenHDO3A).H2O, onde
PhenHDO3A é (rel-10-[(5R,6R)-5,6-dihidro-6-hidroxi-1,10-fenantrolina-5-
il)-1,4,7,10-tetraazaciclododecano-1,4,7-ácido triacético).
Para isso, elaboramos e executamos um procedimento que envolve
o mapeamento ou amostragem do espaço conformacional desses
compostos através de dinâmicas moleculares curtas em diferentes
temperaturas para em seguida, essas geometrias serem usadas como
pontos de partida para otimização de geometria usando tanto o método
semi-empírico AM1 quanto o modelo Sparkle/AM1.
Como resultado, podemos citar que a elevada flexibilidade dos
ligantes macrocíclicos não coordenados DOTA e H4DOTA, serviu para
testar a capacidade da nossa metodologia de visitar regiões distintas do
espaço conformacional.
Para o complexo [Gd(DOTA)H2O]-, conseguimos encontrar os
mesmos isômeros conformacionais que já são reportados em outros
estudos, bem como revelar detalhes relativos à mobilidade da molécula de
água coordenada. Além disso, conseguimos identificar mínimos locais
intermediários que estão relacionados com a dinâmica de rotação dos
grupos acetato em ambos os complexos e a dinâmica de inversão do anel
tetraazadodecano no complexo Gd(PhenHDO3A).H2O.
A relevância desse trabalho está apoiada no fato de que agora
temos uma estratégia interessante para realizar a busca de isômeros
conformacionais desses compostos, sendo essas informações, muito
importantes quando se deseja projetar uma nova molécula para atuar
como agente de contraste em MRI.
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Organofosforové deriváty pro "click-chemistry" / Organophosphorus derivatives for "click-chemistry"Zemek, Ondřej January 2013 (has links)
Ondřej Zemek Organophosphorus derivatives for "click-chemistry" In this diploma thesis two new macrocyclic ligands were synthesized. They have DO3A moiety where metal (lanthanide) ion can be coordinated and terminal acetylenic or azide group connected through the phosphinic acid. Both terminal acetylenic and azide group should serve for connecting to another molecules or partitions by mean of "click chemistry" i.e. [1,3] copperI catalyzed dipolar cycloaddition between azide and acetylene. In this thesis two ligands, its complexes with some lanthanides as well as its precursors were prepared and characterized. Gd3+ complexes will be further used and studied for potential MRI contrast agents applications.
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Metody akvizice pro DCE-MRI / DCE-MRI Acquisition MethodsKudlička, Petr January 2013 (has links)
In my master’s thesis I describe basics of magnetic resonance measurement. I focus on methods of DCE-MRI with T1 weighting image. I mention some basic contrast agents which are used in MRI imaging. I describe some of pulse sequences which are used in experimental part of my thesis. There I measure contrast in the sample. The measurement is performed in accordance with an acquisition protocol I have proposed. The experiment part was realized on 1.5 T magnet at Masaryk Oncological Institute in Brno. I improved software which is use to research of MR IR TurboFLASH’s data and made software which is use to evaluation perfuse analysis ours measured sequences. At the end I made a discussion about gained facts.
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