Techn. University, Diss., 2003--Dresden.

Techn. Hochsch., Diss., 2003--Aachen.

Oncolytic viruses (OV) are an emerging class of anticancer bio-therapeutics that induce antitumor immunity through selective replication in cancer cells. However, the efficacy of OVs as single agents remains limited. We postulate that resistance to oncolytic virotherapy results in part from the failure of tumor cells to be sufficiently infected. In this study, we provide evidence that in the context of sarcoma, a highly heterogeneous malignancy, the infection of tumors by different oncolytic viruses varies greatly. Similarly, for a given oncolytic virus, productive infection of tumors across patient samples varies by many orders of magnitude. To overcome this issue, we hypothesize that the infection of resistant tumors can be achieved through the use of selected small molecules. Here, we have identified two novel drug classes with the ability to improve the efficacy of OV therapy: fumaric and maleic acid esters (FMAEs) and vanadium compounds. FMAEs are enhancing infection of cancer cells by several oncolytic viruses in cancer cell lines and human tumor biopsies. The ability of FMAEs to enhance viral spread is due to their ability to inhibit type I IFN production and response, which is associated with their ability to block nuclear translocation of transcription factor NF-κB. Vanadium-based phosphatase inhibitors enhance OV infection of RNA viruses in vitro and ex vivo, in resistant cancer cell lines. Mechanistically, this involves subverting the antiviral type I IFN response towards a death-inducing and proinflammatory type II IFN response, leading to improved OV spread, increased bystander killing of cancer cells, and enhanced anti-tumor immune-stimulation. Both FMAEs and vanadium compounds improve therapeutic outcomes of OV treatment in syngeneic tumor models, leading to durable responses, even in models otherwise refractory to OV and drug alone. Overall, we showcased novel avenues for the development of improved immunotherapy strategies.

De manière à répondre à l'accroissement des besoins en uranium, l'exploitation de nouvelles ressources de composition minéralogique variée devient une nécessité. De plus, dans une perspective de développement durable, les procédés d'exploitation et de traitement des minerais d'uranium requièrent une optimisation afin de réduire leur empreinte environnementale. Dans ce but, il est nécessaire d'acquérir des données thermodynamiques fiables relatives aux systèmes d'intérêt, dont en particulier les phosphates et les vanadates d'uranium (VI). Dans ce contexte, une étude multiparamétrique de la dissolution de la méta-torbernite Cu0,8(H3O)0,2(UO2)2(PO4)2,8H2O, de la méta-autunite Ca(UO2)2(PO4)2,6H2O, de la méta-ankoleïte K2(UO2)2(PO4)2,6H2O et de la carnotite K2(UO2)2(VO4)2,3H2O a été entreprise. Dans un premier temps, des analogues à ces quatre phases minérales ont été préparés par différentes méthode, basées sur une voie sèche pour la carnotite et sur des voies humides pour les trois phases phosphatées. Elles ont ensuite été caractérisées d'un point de vue structural, microstructural et chimique. Des structures cristallographiques similaires ont ainsi été mises en évidence au sein desquelles les polyoxoanions (PO43- ou V2O86-) et les groupements uranyle forment des feuillets parallèles entre lesquels s'insèrent les contres cations (Cu2+, Ca2+ ou K+) et les molécules d'eau. Hormis pour la méta-ankoleïte, les analogues synthétiques ont également été comparées à des minerais naturels. Il a ainsi été possible de mettre en évidence des différences d'ordre chimique (présence d'impuretés dans les échantillons naturels) et morphologique (tailles de grains, notamment). La dissolution de ces phases a ensuite été étudiée, tant d'un point de vue cinétique que thermodynamique, à travers des études menées en conditions statiques et dynamiques, dans différents milieux acides (H2SO4, HNO3 et HCl) et à plusieurs températures. Les vitesses de dissolution mesurées sont proches de 1 g.m-2.j-1 pour les quatre phases. Dans les conditions utilisées, la dissolution de la méta-autunite s'est avérée incongruente (précipitation de phosphates d'uranyle), empêchant la détermination des constantes de solubilité. En outre, la dissolution de la méta-ankoleïte a conduit à un échange cationique aboutissant à la formation de solutions solides (H3O)2xK2x-2(UO2)2(PO4)2, 6H2O (0 < x < 2) dont les constantes de solubilité ont pu être calculées. Enfin, les expériences menées sur la méta-torbernite et la carnotite ont conduit à des réactions de dissolution congruentes qui ont permis d'accéder aux données thermodynamiquement d'intérêt telles que leur produit de solubilité et leurs grandeurs standards associées à la dissolution (DrH°, DrG° et DrS°) ou à la formation (DfG° = -6100 ± 5 kJ.mol-1 pour la méta-torbernite et DfG° = -4632 ± 7 kJ.mol-1 pour la carnotite) de chacune de ces phases. Les résultats obtenus montrent que les constantes de solubilité des trois phases phosphatées sont très faibles (10-53 < Ks,0° < 10-45) et ont des valeurs qui diffèrent peu selon la nature du contre cation, en bon accord avec leurs similitudes structurales. D'autre part, la comparaison des grandeurs thermodynamiques déterminées dans ce travail, montre que la carnotite (Ks,0° = 10-63) est plus stable que les phases phosphatées étudiées. La différence observée peut s'expliquer par la structure des feuillets à base de vanadates. Cette étude a ainsi permis d'obtenir des premières valeurs de solubilité pour les phosphates et les vanadates d'uranium(VI) présents dans les gisements d'intérêt économique et d'établir un premier modèle d'estimation de la solubilité pour des phases similaires. Ces données ont également été utilisées lors d'une modélisation en conditions environnementales afin de déterminer la nature des phases susceptibles de se former dans un cas réel (eaux d'un lac proche d'un gisement d'uranium). / In the current context of restart of the nuclear energy, the needs in uranium are expected to increase significantly. Moreover, in a perspective of sustainable development, the exploitation, the treatment and the purification of uranium ores need to be optimized. It is thus necessary to determine reliable thermodynamic data (and especially solubility constants) for the systems of interest, especially uranium(VI) phosphates and vanadates. In this aim, a multiparametric study of the dissolution of meta-torbernite Cu0.8(H3O)0.2(UO2)2(PO4)2.8H2O, meta-autunite Ca(UO2)2(PO4)2.6H2O, meta-ankoleïte K2(UO2)2(PO4)2.6H2O and carnotite K2(UO2)2(VO4)2.3H2O was undertaken.First, analogues of these four minerals were synthesized, based only on dry chemistry process for carnotite or on wet chemistry methods for the phosphate phases. They were then extensively characterized (in terms of structure, microstructure and chemical composition). It particularly highlighted the similar structures of such compounds. The anionic groups (PO43- or V2O86-) and uranyl form parallel layers between which counter cations (Cu2+, Ca2+ or K+) and water molecules are inserted. However, the counter cations present in the interlayer space of the three phosphate phases present different lability. The synthetic phases were also compared to their natural analogues, except for meta-ankoleïte, which allowed us to point out significant differences in the composition (presence of impurities in natural samples) and the morphology (grain size).The dissolution of these phases was then studied from a kinetic and thermodynamic point of view, through leaching tests in static and dynamic conditions, in various acid media (sulfuric, nitric and hydrochloric) and at different temperatures. In these conditions, the dissolution of meta-autunite was found to be uncongruent due to the precipitation of uranyl phosphate then avoidinf the determination of solubility constants. Similarly, the dissolution of meta-ankoleite was preceded by a cation exchange step between K+ and H3O+ leading to the formation of (H3O)2xK2x-2(UO2)2(PO4)2.6H2O (0 < x < 2) solid solutions, whose solubility constant have been evaluated. Finally, meta-torbernite and carnotite presented congruent dissolutions which allowed the determination of thermodynamic data of interest such as solubility products and standard enthalpy, Gibbs free energy and entropy associated with the dissolution reaction (DrH°, DrG° and DrS°) and formation of each phase (DfH°, DfG° and DfS°).The results obtained evidenced very low and similar solubility constants for the three phosphate phases studied (10-53 < Ks,0° < 10-45). Such small variation directly came from the closely related crystal structures previously described. In addition, the difference in composition of the sheets between phosphate and vanadate phases led to greater stability of carnotite (Ks,0° = 10-63) compared to phosphates phases. The solubility values derived from this study for phosphates and vanadates uranium(VI) allowed estimating values for similar phases. These data were also used in a geochemical model for the prediction of neoformed phases in a real case (water of a lake near an uranium deposit).

Charge excitations in different 3d transition metal compounds are studied. In particular, the influence of the lattice geometry on the character of these excitations is investigated. For this purpose, the momentum dependent loss function of electron energy-loss spectroscopy (EELS) as well as the optical conductivity are calculated and compared with the experimental data of NaV$_{2}$O$_{5}$, LiV$_{2}$O$_{5}$, Sr$_{2}$CuO$_{3}$, and CuGeO$_{3}$ . A quarter-filled extended Hubbard model on a system of coupled ladders provides a qualitative explanation for the highly anisotropic charge excitations of NaV$_{2}$O$_{5}$ and LiV$_{2}$O$_{5}$. These ladder compounds do not only differ from the charge ordering pattern but also from the coupling between different ladders: In LiV$_{2}$O$_{5}$ one finds a strong inter-ladder hopping which is very small in NaV$_{2}$O$_{5}$. On the other hand, in NaV$_{2}$O$_{5}$ the ladders are coupled by a strong inter-ladder Coulomb interaction. The charge excitations of quasi one-dimensional cuprates reflect both the properties of the CuO$_{4}$ plaquettes and the character of the coupling between different plaquettes. Independently from the geometry of the cuprat chains, the local excitation of the copper hole onto the adjacent oxygen orbitals is always found. Further transitions with an excitation energy below the local excitation of a single plaquette result from a hole transfer to another plaquette. These excitations with hole delocalization dominate the spectra of the corner-shared Sr$_{2}$CuO$_{3}$. In contrast to this, the hole transfer leads only to a pre-peak in the spectra of the edge-shared CuGeO$_{3}$. Furthermore, it is shown that the hole transfer is determined by the geometry of the edge-shared CO. / Gegenstand dieser Arbeit ist die theoretische Analyse von Ladungsanregungen in verschiedenen niedrigdimensionalen 3d-Übergangsmetallverbindungen, wobei insbesondere der Einfluß der Gittergeometrie auf die Charakteristik der Anregungen untersucht wurde. Mit Hilfe des Lanczos-Algorithmus' wurden dazu sowohl die impulsabhängige Verlustfunktion der Elektron-Energie-Verlust-Spektroskopie (EELS) als auch die optische Leitfähigkeit für NaV$_{2}$O$_{5}$, LiV$_{2}$O$_{5}$, Sr$_{2}$CuO$_{3}$ und CuGeO$_{3}$ berechnet und mit den experimentellen Ergebnissen verglichen. Unter der Verwendung eines Modells viertelgefüllter Leitern kann man die Ladungsanregungen sowohl für NaV$_{2}$O$_{5}$ als auch LiV$_{2}$O$_{5}$ sehr gut beschreiben. In diesen Materialien findet man nicht nur unterschiedliche Ladungsordnungen sondern vor allem auch verschiedene Kopplungsarten zwischen den Leitern. Während die Leitern im NaV$_{2}$O$_{5}$ durch die Coulomb-Wechselwirkung miteinander gekoppelt sind, existiert im LiV$_{2}$O$_{5}$ ein Austausch aufgrund einer starken Hybridisierung zwischen den Leitern. Die Ladungsanregungen von quasi eindimensionalen Kupratketten spiegeln sowohl die Plaketteneigenschaften als auch die Plakettenkopplung wider. Unabhängig von der Geometrie der Ketten findet man stets die lokale Anregung des Kupferloches auf die umliegenden Sauerstofforbitale. Aus einem möglichen Lochtransfer zu benachbarten Plaketten resultieren außerdem noch Anregungen, die energetisch unterhalb der Plakettenanregung liegen und unmittelbar von der Kettengeometrie abhängen. Während im eckenvernetzten Sr$_{2}$CuO$_{3}$ diese Anregungen die Spektren dominieren, spielt der Lochtransfer im kantenvernetzten CuGeO$_{3}$ nur eine untergeordnete Rolle.

Charge excitations in different 3d transition metal compounds are studied. In particular, the influence of the lattice geometry on the character of these excitations is investigated. For this purpose, the momentum dependent loss function of electron energy-loss spectroscopy (EELS) as well as the optical conductivity are calculated and compared with the experimental data of NaV$_{2}$O$_{5}$, LiV$_{2}$O$_{5}$, Sr$_{2}$CuO$_{3}$, and CuGeO$_{3}$ . A quarter-filled extended Hubbard model on a system of coupled ladders provides a qualitative explanation for the highly anisotropic charge excitations of NaV$_{2}$O$_{5}$ and LiV$_{2}$O$_{5}$. These ladder compounds do not only differ from the charge ordering pattern but also from the coupling between different ladders: In LiV$_{2}$O$_{5}$ one finds a strong inter-ladder hopping which is very small in NaV$_{2}$O$_{5}$. On the other hand, in NaV$_{2}$O$_{5}$ the ladders are coupled by a strong inter-ladder Coulomb interaction. The charge excitations of quasi one-dimensional cuprates reflect both the properties of the CuO$_{4}$ plaquettes and the character of the coupling between different plaquettes. Independently from the geometry of the cuprat chains, the local excitation of the copper hole onto the adjacent oxygen orbitals is always found. Further transitions with an excitation energy below the local excitation of a single plaquette result from a hole transfer to another plaquette. These excitations with hole delocalization dominate the spectra of the corner-shared Sr$_{2}$CuO$_{3}$. In contrast to this, the hole transfer leads only to a pre-peak in the spectra of the edge-shared CuGeO$_{3}$. Furthermore, it is shown that the hole transfer is determined by the geometry of the edge-shared CO. / Gegenstand dieser Arbeit ist die theoretische Analyse von Ladungsanregungen in verschiedenen niedrigdimensionalen 3d-Übergangsmetallverbindungen, wobei insbesondere der Einfluß der Gittergeometrie auf die Charakteristik der Anregungen untersucht wurde. Mit Hilfe des Lanczos-Algorithmus' wurden dazu sowohl die impulsabhängige Verlustfunktion der Elektron-Energie-Verlust-Spektroskopie (EELS) als auch die optische Leitfähigkeit für NaV$_{2}$O$_{5}$, LiV$_{2}$O$_{5}$, Sr$_{2}$CuO$_{3}$ und CuGeO$_{3}$ berechnet und mit den experimentellen Ergebnissen verglichen. Unter der Verwendung eines Modells viertelgefüllter Leitern kann man die Ladungsanregungen sowohl für NaV$_{2}$O$_{5}$ als auch LiV$_{2}$O$_{5}$ sehr gut beschreiben. In diesen Materialien findet man nicht nur unterschiedliche Ladungsordnungen sondern vor allem auch verschiedene Kopplungsarten zwischen den Leitern. Während die Leitern im NaV$_{2}$O$_{5}$ durch die Coulomb-Wechselwirkung miteinander gekoppelt sind, existiert im LiV$_{2}$O$_{5}$ ein Austausch aufgrund einer starken Hybridisierung zwischen den Leitern. Die Ladungsanregungen von quasi eindimensionalen Kupratketten spiegeln sowohl die Plaketteneigenschaften als auch die Plakettenkopplung wider. Unabhängig von der Geometrie der Ketten findet man stets die lokale Anregung des Kupferloches auf die umliegenden Sauerstofforbitale. Aus einem möglichen Lochtransfer zu benachbarten Plaketten resultieren außerdem noch Anregungen, die energetisch unterhalb der Plakettenanregung liegen und unmittelbar von der Kettengeometrie abhängen. Während im eckenvernetzten Sr$_{2}$CuO$_{3}$ diese Anregungen die Spektren dominieren, spielt der Lochtransfer im kantenvernetzten CuGeO$_{3}$ nur eine untergeordnete Rolle.

Thesis (PhD (Physics))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: The output power of end-pumped lasers is mainly limited by thermal effects in the bulk crystal gain material. The thermal effects either fracture the crystal or cause degradation in the laser beam quality and output power. This is especially pronounced in Nd:YVO4 and Nd:GdVO4 which exhibit strong thermal lensing. These two Nd3+ vanadate materials are of great value because of their high emission cross sections which makes them excellent gain materials for mode-locked, high repetition rate Q-switched and intra-cavity frequency doubled lasers. The two Nd3+ vanadates have very similar spectral properties but many publications claim that the more expensive Nd:GdVO4 is thermo-optically superior to Nd:YVO4. However, a debate ensued after theoretical calculations as well as measurements of the thermal conductivity and thermo-optical coefficients indicated that the opposite is true. To our knowledge there has never been a direct comparison of the thermal lensing of these two materials under identical pumping and lasing conditions. In order to contribute to the debate we did such measurements for different crystals of these two materials with equal low doping using three different measurement methods. We subsequently determined that Nd:YVO4 has slightly lower thermal lensing for the stronger gain -polarisation. One of the measurement methods we used is a novel more reproducible one that we developed for this purpose. It is more reproducible because it selectively measures only the focal length of the central, relatively unaberrated part of the thermal lens. Another measurement, utilising a probe beam through the laser crystal, found that there was almost no increase in the temperature when lasing is interrupted. This indicated that there is almost no upconversion present in the crystals which is probably due to their optimally chosen low doping. A further consequence of the vanadate debate is that there is still confusion about the value of the important thermo-optical coefficient for the higher gain -polarisation (dne/dT ) of Nd:YVO4. This parameter is of great importance in thermal calculations since the strength of the thermal lens is largely dependent on it. We therefore numerically modelled the thermal lensing in our crystals using different dne/dT values and found that the value given by Sato & Taira (2007) matches our experimental results the best. Our measurements also indicated that the thermal lens dioptric power increased nonlinearly with pump power. This appeared to contradict theory of thermal lensing since we knew that there was no upconversion in the crystals (which is the standard explanation for the nonlinear increase). We proceeded to use our numerical modelling to identify the main source of the nonlinear increase as the varying spectral output of the diode pump laser. The findings in this thesis therefore extend knowledge of the thermo-optical properties of the vanadates and increase understanding of the strongly aberrated thermal lenses formed inside them. Furthermore, the findings now enable the power-scaling of end-pumped vanadates lasers to higher levels. / AFRIKAANSE OPSOMMING: Die uitset drywing van longitudinale-gepompte vaste-toestand lasers word hoofsaaklik beperk deur termiese effekte in die laser kristal. Die kristal word of gekraak of die laser se bundel kwaliteit en uitset drywing verminder. Dit is veral ’n problem in Nd:YVO4 en Nd:GdVO4 kristalle waarin sterk termiese lense voorkom. Hierdie twee Nd3+ vanadaat kristalle is waardevol vanwee hulle ho¨e emissie deursnitte wat hulle uitstekend maak as versterkings materiale vir modus-gesinkroniseerde, ho¨e repitisie, Q-geskakelde en binne-resonator frekwensie-verdubbelde lasers. Die twee vanadate het baie soortgelyke spektrale eienskappe, maar verskeie publikasies beweer dat die duurder Nd:GdVO4 materiaal termo-opties beter is as Nd:YVO4. Onlangse teoretiese berekeninge asook metings van die termiese en termo-optiese kwaliteite van die twee kristalle toon egter die teenoorgestelde. Sover ons weet is daar nog geen direkte vergelyking van die termiese lens in hierdie twee materiale onder identiese kondisies gedoen nie. Ons het dus so ’n meting aangepak vir kristalle met identiese lae konsentrasie van die Nd3+ ioon deur drie verskillende meet metodes te gebruik. Een van die meet metodes is ’n nuwe, meer reproduseerbare metode wat ons ontwikkel het vir hierdie doel. Dit is meer reproduseerbaar omdat dit slegs die binneste deel van die termiese lens meet wat min sferiese aberrasie het. ’n Ander meeting, wat ’n toets-bundel deur die kristal stuur, het getoon dat daar byna geen verhoging in die die temperatuur van die kristal was toe ossilasie in die resonator onderbreek was nie. Dit is ’n aanduiding dat dat daar byna geen op-omskepping teenwoordig is in die kristalle nie wat te danke is aan hul optimale lae konsentrasie van die Nd3+ ioon. ’n Verdere gevolg van die debat is dat daar nog verwarring in die literatuur bestaan oor die waarde van Nd:YVO4 se termo-optiese dne/dT koeffisi¨ent. Hierdie parameter is van groot belang in berekinge van die termiese lens se fokale lengte vir die ho¨er wins -polarisasie. Deur numeriese modellering te gebruik het ons bevind dat die waarde wat verskaf word deur Sato & Taira (2007) ons eksperimentele data die beste pas. Ons metings het ook aangedui dat die dioptriese krag van die termiese lens nie linie¨er toeneem ten opsigte van die geabsorbeerde pomp krag nie. Dit was o¨enskynlik teenstryding met teorie oor termiese lense. Dit is omdat ons bevestig het dat daar geen op-omskepping in die kristalle teenwoordig was nie, wat die standaard verklaring vir die nie linie¨eriteit is. Ons het dus ons numeriese modellering gebruik om die hoofbron van die nie-lini¨ere toename te identifiseer as die veranderende spektrale uitset van die diode pomp laser. Die bevindings in hierdie tesis bou dus kennis op oor die termo-optiese eienskappe van die vanadate en versterk begrip van die sterk termiese lense binne hulle. Verder stel die bevindings ons nou in staat om die uitset drywing van longitudinale-gepompte vanadaat lasers na ho¨er vlakke te skaal.

The ability to encapsulate/insert different kinds of nanoparticles (NPs) in scrolled nanosheets (NSs) may lead to the formation of new nanocomposite materials that yield novel properties. These nanostructures resemble “peapods” that consist of NPs chains (“peas”) located in a hollow space of desired nanoscrolls (“pods”). Depending on different combinations of “peas” and “pods” diverse families of nanopeapods (NPPs) can be synthesized which may exhibit interesting properties not accessible from the individual components. Though there exist various synthetic methods for the formation of NPPs, more development in terms of simplicity, flexibility, and productivity of synthetic approaches are needed so that different classes of NPPs with unique combinations/characteristics of “peas” and “pods” can be synthesized. A simple solvothermal synthesis method for the encapsulation of spherical Fe3O4 NPs by the capture of preformed NPs in scrolled hexaniobate has previously been developed in our group. In the first part of this research, efforts were made to extend the “pod” materials to other inorganic NScs. Vanadate nanoscrolls (NScs) could rapidly (2h) be produced using a simple solvothermal treatment in the presence of V2O5 as vanadium source, and either dodecylamine (DDA) or octadecylamine (ODA) as the structure-directing agent. The synthesis parameters were successfully adjusted to obtain high yields vanadate NScs (~ 20 g of NScs per synthesis) with different average lengths as 383 nm, 816 nm to 3.3 µm. The effects of reaction time on the formation of NScs were also investigated. Further efforts focused on the development of methods for making vanadate NPPs. Here, two novel approaches for the formation of these NPPs have been successfully developed. In the first, solvothermal methods utilizing preformed Ag NPs and vanadate NSs lead to the formation of Ag@vanadate NPPs where NPs could be encapsulated during the scrolling of NSs. High NP loadings were acquired with this approach. In the second method, an insertion strategy was developed where Ag NPs were drawn into the lumen of preformed vanadate NScs upon controlled solvent evaporation. This method was also quite effective, though much lower loadings of NPs were achieved with larger average NP-NP distances. Also noteworthy in the study of vanadate NScs and NPPs is the observation of an uncommon asymmetric scrolling behavior; this was realized for both vanadate NScs and solvothermally synthesized Ag@vanadate NPPs. Novel solvothermal approaches for the effective construction of organic-MoOx hybrid structures and MoOx nanosheets (NSs) have also been developed. These NSs can be controlled so as to exist in different oxidation states as well as in different crystal structures. Layer spacing as a function of organic molecule lengths could also be controlled by changing the type of surfactants located between the NSs. Individual NSs or a few layers of stacked NSs, up to four micrometers in lateral size were successfully prepared upon sonication. The effect of time, temperature, as well as the type of structure-directing agents on the formation and crystal structure of MoOx intercalated compound/NSs were also explored. Lastly, a modified solvothermal method previously used for the encapsulation of spherical Fe3O4 NPs inside hexaniobate NScs was applied for the construction of cubic-CeO2 NPPs. High yield encapsulations of preformed cubic ~5 nm ceria NPs within the lumen of hexaniobate NScs were readily accomplished. Size selective encapsulation and the formation mechanism of cubic-CeO2 NPPs were also studied. Pre-organization and attachment of ceria NPs to the surface/edges of hexaniobate crystals prior to the scrolling process were observed, which is in a good agreement with our previous studies on the formation mechanism of NPPs. Partially filled CeO2@hexaniobate NPPs were further used in the in-situ growth of gold NPs within the empty/hollow space of hexaniobate NScs. This led to the formation of high-quality Au-CeO2@hexaniobate NPPs. We believe that smart combinations of the methods for the formation of NPPs, encapsulation, in-situ growth and insertion, will allow one to acquire other classes of nanocomposite materials composed of different types, shapes, and arrangements of NPs in the hollow spaces of distinct NTs/NScs.

Os altos índice de sucesso dos implantes dentais e sua indicação crescente apresentam como limitação a contaminação bacteriana com a consequente doença peri-implantar. Os métodos de tratamento ainda não se apresentam claros e seguros, portanto, meios de prevenção que impeçam a formação de biofilme e inibam o crescimento bacteriano devem ser desenvolvidos e aplicados para impedir a falha dos implantes. O objetivo deste estudo foi avaliar a efetividade de um novo antimicrobiano nanoparticulado - o vanadato de prata (AgNO3) em diferentes concentrações (2,5%; 5% e 10%), aplicado sob a forma de filme superficial sobre diferentes substratos sugeridos para dispositivos da Implantodontia. Foram selecionados os materiais poliacetal, teflon e resina acrílica e os veículos glaze e esmalte para a aplicação do nanocomposto. Análises das propriedades físicas rugosidade superficial e dureza Rockwell superficial, assim como imagens obtidas por meio da Microscopia Eletrônica de Varredura (MEV), foram utilizadas para avaliar a resistência e alterações estruturais dos grupos e portanto, a viabilidade de aplicação clínica. A análise pelo método microbiológico do halo de inibição mostrou que as bactérias P. aeruginosa, E. coli, S mutans, E. faecalis e S. aureus tiveram inibição de crescimento; enquanto nas bactérias anaeróbias P. gingivalis e P. intermedia e na levedura C. albicans não foi demonstrada a atividade antibacteriana de AgNO3. O tipo de substrato utilizado e de veículo para a aplicação de AgNO3 não influenciaram nos resultados, com exceção do S. aureus que obteve maior diâmetro do halo de inibição quando aplicado com o glaze em comparação ao esmalte (p<0,05). A proporção do nanocomposto mostrou influência nos resultados, sendo que 10% se mostrou a mais eficaz em todas as bactérias, e de modo geral sem diferença estatística com a proporção de 5% (p<0,05). Apesar de proporções menores algumas vezes não mostrarem atividade antimicrobiana, estas provocaram menor alteração nas propriedades físicas dos materiais, sendo a proporção do AgNO3 proporcional ao aumento da rugosidade e dureza superficial. Os substratos e tipo de filme não influenciaram nos resultados da rugosidade superficial após a aplicação do tratamento superficial (p>0,05), entretanto a aplicação de 10% do nanocomposto causou a alteração superficial mais significativa (7,02 ± 2,99 Ra) (p<0,05). Na dureza superficial não foi encontrada alteração significativa com o aumento da concentração do AgNO3 no poliacetal e na resina acrílica (p>0,05), no entanto no teflon, 10% de AgNO3 não alterou significativamente os valores de resistência. Apesar dos filmes não influenciarem nos resultados, o substrato poliacetal demonstrou maior dureza com diferença estatística com os demais substratos (83,0 ±10,2 HR15Yadaptado) (p<0,05). As imagens obtidas no MEV comprovaram mudanças estruturais superficiais com a presença de mais picos e vales, em comparação a superfícies sem o tratamento antimicrobiano. Como conclusão, apesar de 10% ser a concentração do AgNO3 que atingiu um maior número de espécies, essa concentração deve ser ponderada sobre o seu uso, e avaliada em estudos futuros sobre a sua viabilidade de uso clínico em função das alterações nas propriedades físicas. / The high success rate of dental implants and their growing indications show the limitation of bacterial contamination with consequent peri-implant disease. The treatment methods have not yet clear and secure, thus means for preventing the deposition of biofilm and inhibit bacterial growth must be developed and implemented to prevent failure of implants. The aim of this study was to evaluate the effectiveness of a new nanoparticulate antimicrobial - vanadate silver (AgNO3) in different concentrations (2.5%, 5% and 10%), applied as a surface film on different substrates suggested for devices of Implantology. The materials polyacetal teflon and acrylic resin and vehicles enamel / glaze were selected for the application of nanocomposite. Analyzes of the physical properties surperficial roughness and superficial hardness Rockwell, as well as images obtained by scanning electron microscopy (SEM) were used to assess the strength and structural changes of the groups and therefore the feasibility of clinical application. A microbiological method for the analysis of inhibition zone shows growth inhibition on the bacterias P. aeruginosa, E. coli, S. mutans, E. faecalis and S. aureus; while the anaerobic bacteria P. gingivalis and P. intermedia and the yeast C. albicans has not been demonstrated antibacterial activity of AgNO3. The type of substrate used and the vehicle for the application of AgNO3 did not influence the results, with the exception of S. aureus with highest diameter of inhibition zone when applied with glaze compared to enamel (p<0.05). The proportion of the nanocomposite showed influence on the results, 10% proved the most effective in all bacteria, and generally no statistical difference in the proportion of 5% (p<0.05). Although smaller proportions sometimes do not show antimicrobial activity, these caused minor change in the physical properties of materials. The ratio of AgNO3 was proportional to the increase of roughness and hardness. The substrates and film type did not influence the results of the surface roughness after applying the surface treatment (p>0.05), however the application of 10% of the nanocomposite caused surface alteration more significant (7.02 ± 2.99 Ra) (p<0.05). In hardness was not found to significantly change with concentration of AgNO3 in the acrylic resin and the polyacetal (p> 0.05). However in teflon, 10% AgNO3 did not significantly alter the resistance values. Although the films do not influence the results, polyacetal substrate showed higher hardness with statistical difference with the other substrates (83.0 ± 10.2 HR15Yadaptado) (p <0.05). The SEM images proved superficial structural changes with the presence of more peaks and valleys compared to surfaces without antimicrobial treatment. In conclusion, despite 10% being the concentration of AgNO3 that reached the highest number of species, this concentration should be thought on its use, and evaluated in future studies on the feasibility of clinical use in accordance with changes in physical properties.

Les espèces dérivées de l'oxygène comme le peroxyde d'hydrogène jouent un rôle déterminant dans le bon fonctionnement des cellules en tant que molécule de signalisation dans de nombreux processus cellulaires. Les fortes concentrations pouvant être nocive, la régulation de ces substances est vitale. Leur détection résolue en temps est longtemps restée un défi pour la compréhension des mécanismes cellulaires et l'élaboration de traitements efficaces pour des maladies comme l'hypertension ou l'athérosclérose. Ce travail de thèse a ainsi été consacré au développement d'un nouveau type de capteur de substances oxydantes à base de nanoparticules de va- nadate d'Yttrium dopé par de l'Europium. Ces nanoparticules peuvent être internalisées dans les cellules et permettent une détection temporelle de la concentration en peroxyde d'hydrogène dans un domaine étendu de concentrations (1 μM à 5 mM). Après une calibration préalable, ces nanoparticules ont permis de détecter la production de peroxyde d'hydrogène dans les mécanismes de signalisation dans des cellules musculaires lisses vasculaires de souris liés à l'endothéline-1 et au facteur de croissance dérivé des plaquettes. Cette étude comparative a montré deux dynamiques différentes de la production de peroxyde d'hydrogène. Ces dynamiques distinctes peuvent expliquer au moins partiellement la différence de comportement cellulaire.