Low-dimensional magnetic systems are of interest due to several new effects and modifications that occur at sizes below the average domain grain boundary within the bulk material. Molecule-like magnetite (Fe3O4) nanoparticles, with sizes ranging from one to two nm were synthesized and characterized in order to investigate new properties arising from quantum size effects. These small systems will provide opportunities to investigate magnetism of zero-dimension systems. A zero-dimensional object is usually called a quantum dot or artificial atom because its electronic states are few and sharply separated in energy, resembling those within an atom. Since the surface to volume ratio is the highest for zero-dimensional systems, most of the changes to magnetic behavior will be observed in ultra-fine magnetic particles. Chemically functional magnetic nanoparticles, comprised of a Fe3O4 magnetite core encased in a thin aliphatic carboxylate, have been prepared by sequential high temperature decomposition of organometallic compounds in a coordinating solvent. In this work, aliphatic carboxylic acid chain length, reaction temperature and duration were varied to produce small core diameters. In order to correlate size effects with changes in particle formation, it is important to have a through understanding of the structural components. This includes studies of the core size, surface effects, decomposition, electronic properties and magnetic behavior. Quantum size effects were observed in the (Fe3O4)X(carboxylate)Y monolayer protected clusters (MPCs) when the average core diameter was ≤ 2.0 nm, evidenced by a blue shifted absorbance band maxima, suggesting the onset of quantum confinement. These (Fe3O4)X(carboxylate)Y MPCs also posses a complex interplay between surface and finite size effects, which govern the magnetic properties of these zero-dimensional systems. These MPCs are all superparamagnetic above their blocking temperatures with total magnetic anisotropy values greater than the bulk value due to an increase in surface and magnetocrystalline anisotropy. A non-linear decrease in saturation magnetization (MS) [Bohr Magneton] per cluster) as a function of the reciprocal of core radius have been attributed to surface effects such as a magnetically inactive layer or an increase in spin disorder as core diameter decreases. The reduced core dimensions of these MPCs make them ideal candidates for further investigation of quantum magnetic systems.

Made available in DSpace on 2014-10-09T12:26:42Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:04:31Z (GMT). No. of bitstreams: 0 / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Made available in DSpace on 2014-10-09T12:26:42Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:04:31Z (GMT). No. of bitstreams: 0 / Com uma área plantada de cerca de 21 milhões de hectares, e uma produção anual de 60 milhões de toneladas em 2008, o Brasil é hoje o segundo maior produtor de soja no mundo, com pouco mais de um quarto da produção mundial. A presença de flavonóides, em particular isoflavonas em produtos de soja, tem sido relatada como importante para a saúde humana. Foi sugerido também que esses compostos estariam envolvidos na proteção contra a radiação UV de componentes celulares vitais das plantas. A espectroscopia por ressonância paramagnética eletrônica (RPE) pode medir radicais livres resultantes do processo de irradiação. A RPE tem sido empregada com sucesso na detecção de certos produtos comestíveis irradiados. Ao todo vinte e uma cultivares brasileiras de soja, provenientes de duas safras, tratadas por radiação gama de 60Co foram estudadas através de RPE. Foi calculada a correlação entre os teores parciais e totais de isoflavonas e a intensidade do pico central observado nos espectros de RPE (fator g = 2,0039). Não houve correlação entre o sinal e os teores totais de isoflavonas, mas observou-se correlações negativas com gliciteína e acetil-daidzina. Mesmo após 7 meses da irradiação, a intensidade do sinal central de RPE manteve-se a ponto de poder identificar amostras irradiadas. Espectros com partes da soja, particularmente o hilo e a casca, mostraram-se mais eficientes do que aqueles com o grão todo para serem utilizados na identificação de soja irradiada. A radiação não alterou de modo significativo os teores totais de isoflavonas, embora haja indícios de que alguma conversão da forma glicosilada para a aglicona tenha ocorrido. / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Les nanoparticules AGuIX® sont des petites plateformes paramagnétiques qui ont été développées pour des applications en imagerie médicale. Ces nanoparticules se composent à leur surface de plusieurs fonctions amines utilisées pour le greffage de ligands Gd-DOTAGA. Ces nanoparticules paramagnétiques ont un diamètre inférieur à 5 nm. Différentes études dans le domaine du cancer ont montré que ces nanoparticules disposaient de propriétés théragnostiques, permettant à la fois la réalisation d'un diagnostic et d'une thérapie. En effet, la surface rigide des AGuIX permet une multimodalité dans l'usage des techniques d'imagerie médicale. Par ailleurs, leur faible diamètre hydrodynamique assure un ciblage tumoral passif par effet EPR (Enhanced Permeability and Retention) et la présence de Gd permet la réalisation de radiothérapies guidées plus localisées au niveau tumoral. Par ailleurs, leur taille permet une excrétion du corps rapide par la voie rénale. La vitesse de transmétallation relativement faible des ions Gd3+ complexés par les ligands DOTA, en présence d'ions métalliques tels que le Zn2+, assure des effets toxicologiques négligeables dans le cadre d'études précliniques. Des études ont montré que le peptide TLVSSL a une forte affinité pour la phosphatidylsérine, un phospholipide surexposé sur des cellules en processus de mort cellulaire par apoptose. Le ciblage des cellules apoptotiques est intéressant dans le cadre du suivi de l'efficacité d'une thérapie anti-tumorale mais aussi pour le diagnostic des maladies liées à ce processus. Dans ce travail, les nanoparticules AGuIX ont ainsi été greffées avec ce peptide (AGuIX-E3) pour ensuite être caractérisées. Pour augmenter la mobilité des peptides fixés à la surface de la plateforme rigide, les AGuIX ont également été greffées avec des peptides liés à un linker, l'acide 8-amino-3,6-dioxaoctanoïque, par l'intermédiaire d'une liaison amide (AGuIX-L-E3), mais également avec un peptide scramble (AGuIX-E3Sc, AGuIX-L-E3Sc).Les nanoparticules AGuIX® ont été greffées avec le peptide en considérant l'activation préalable des fonctions carboxyliques disponibles en surface avec de l'EDC. En outre, l'addition d'un marqueur fluorescent (rhodamine ou cyanine 5.5) a été réalisée afin de permettre des applications en microscopie de fluorescence, FACS et imagerie optique. Plusieurs techniques de caractérisations physico-chimiques telles que PCS, la spectroscopie de fluorescence, l'HPLC et la relaxométrie protonique ont été réalisées pour étudier ces plateformes. Des mesures relaxométriques et la réalisation de profils Nl\IRD ont confirmé l'augmentation du temps de corrélation rotationnelle après la fixation du peptide et ont aussi permis d'étudier la stabilité des nanoparticules en fonction du temps. Des tests biologiques sur cellules effectués en utilisant les techniques de microscopie à fluorescence, de cytométrie en flux ainsi que de relaxométrie, ont permis de déterminer l'affinité des nanoparticules pour les phosphatidylsérines surexposées à la surface d'une lignée de cellules T humaines lymphoblastiques (.Jurkat) au cours du processus de mort cellulaire. L'apoptose a été chimiquement induite par le traitement préalable des cellules avec de la camptothécine, un composé chimique connu pour ses propriétés anti-tumorales. Cependant, bien que les analyses in vitro ont confirmé l'impact réel du greffage des AGuIX sur l'efficacité de ciblage de l'apoptose, des études in vivo n'ont pas montré une influence significative du peptide lors de l'injection des nanoparticules (AGuIX, AGuIX-E3, AGuIX-E3Sc) sur un modèle de souris traitées avec de la dexaméthasone (DEX). En effet, la DEX a. fait l'objet d'études qui montrent son influence dans le déclenchement d'une apoptose cellulaire au niveau du thymus. En conclusion, plusieurs caractérisations chimiques et des tests biologiques réalisés lors de nos recherches ont confirmé le greffage des peptides E3 et E3Sc sur les nanoparticules AGuIX / AGuIX® nanoparticles are small platforms of polysiloxane developed for applications in medical imaging. These nanoparticles present on their surface several amine functions used for the grafting of Gd-DOTA complexes. These paramagnetic platforms have a diameter less than 5 nm. Different studies have been achieved showing that they allow to combine multimodal diagnosis and theranostic properties with a passive tumoral targeting observed by EPR effect (Enhanced Permeability and Retention). Otherwise, their small size allows a quick body excretion by the kidneys. The low transmetalation rate of Gd3+ ions complexed by DOTA provides negligible toxicological effects in pre-clinical studies.Some studies showed that TLVSSL peptide has a high affinity for phosphatidylserine, a phospholipid overexposed on cells in apoptosis process of death. The targeting of apoptotic cells is interesting to follow the efficiency of an antitumoral therapy and for diagnosis of diseases related to this process. In this work, AGuIX nanoparticles have thus been grafted with this peptide and characterized (AGuIX-E3). To increase the peptide mobility against the rigid platform, AGuIX were also grafted with peptides bound to a linker through an amide bond with 8-amino-3,6-dioxaoctanoic acid, (AGuIX-L-E3) and with a peptide scramble (AGuIX-E3Sc, AGuIX-L-E3Sc).AGuIX® nanoparticles were grafted with peptide by activation with EDC of the carboxylic functions available on nanoparticle surface. Furthermore, previous addition of an optical dye allows their applications in optical imaging (rhodamine or cyanine 5.5). Different physicochemical techniques such as PCS, fluorescence spectroscopy, HPLC and proton relaxometry were used to characterize these platforms. Relaxometric studies by NMRD profiles confirmed the increase of the rotational correlation time after linking of peptide and allow to study the time stability of the platform. Biological tests were performed using fluorescence microscopy, relaxometry and flow cytometry techniques to determine the affinity of nanoparticles for lymphoblastic human T cell line (Jurkat) cells overexposing phosphatidylserine, suggesting an efficiency to target apoptosis. In vitro cell apoptosis was chemically induced by incubation with campthothecin. However, though in vitro analysis confirmed the real impact of the grafting of AGuIX on the efficiency to target apoptosis, first in vivo studies didn’t showed a significant influence of peptide when nanoparticles (AGuIX, AGuIX-E:), AGuIX-E3Sc) were injected on mice. Injected-mice were previously treated with dexamethasone to trigger apoptosis in thymus. In conclusion, several chemical characterizations and biological tests achieved on our research confirmed the binding of peptides on AGuIX nanoparticles. In vitro analyses have showed an efficient targeting of cells with overexposed phosphatidylserine by grafted­AGuIX nanoparticles. Nevertheless, in vivo experiments didn't confirm the conclusion suggested in vitro tests. Indeed, the intake of active targeting of apoptotic cells by grafted­AGuIX is not relevant in front of the non-specific targeting observed with non-grafted AGuIX. Further in vivo tests should be however achieved to confirm these observations