Des nanoparticules d’or fonctionnelles ont été synthétisées avec pour objectifs l’élaboration de nanomatériaux pour applications biomédicales et propriétés physiques originales. L’étude de la fonctionnalisation a conduit à utiliser le chimie “click” entre des nanoparticules d’or portant des ligands thiolates azoturés et des alcynes terminaux en utilisant un catalyseur au cuivre (I) renforcé par un ligand polyazoté, ce qui a permis d’introduire des fonctions très variées. En particulier le récepteur folate a été greffé de cette façon pour la synthèse de nouveaux vecteurs du docétaxel, un puissant agent anti-cancéreux dont l’étude est menée en collaboration. Des nanoparticules d’or fonctionnelles ont aussi servi de support pour le greffage de complexes du fer (II) à transition de spin, ce qui a permis de réaliser l’étude en 2D par différentes techniques physiques en collaboration. Enfin un nouveau ligand azoté a été mis au point pour la synthèse de nanoparticules d’or originales. / The thesis concerns functionalizations and applications of gold nanoparticles (AuNPs). In the aspects of functionalization of AuNPs, we concentrated on efficiently functionalized AuNPs by “Click” chemistry. In the aspects of applications, the PEG capped AuNPs was prepared to encapsulate vitamins, which has a potential use in hydrophobic part of human body; the folate functionalized AuNPs was used for docetaxel delivery for cancer therapy; the novel synthesis of triazole stabilized AuNPs used for biosensors; and the citrate capped AuNPs introduced into the silica thin films to check the SERS effect and spin crossover of iron complexes.

A series of oxide materials were modified with different nanoparticles (NPs). Novel cobalt@H4Nb6O17 nanopeapod structures were fabricated and magnetic NPs modified oxide nanosheets and nanoscrolls were prepared. Both aqueous method and two-phase method were applied to prepare gold NPs onto oxide nanosheets, nanoscrolls and other nanocrystals. The combination of H4Nb6O17 nanoscrolls and cobalt NPs generate a novel method to fabricate nanopeapod structures. Cobalt NPs were synthesized in the presence of exfoliated H4Nb6O17 nanosheets and the resulting magnetic chain structures, formed due to the dipole-dipole interaction, were captured within scrolled lamella. The yield of peapod structures can be improved by using proper reagents and reaction temperatures. As similar method with iron oxide NPs also produced peapod-like structures in a low yield. Exfoliated Dion-Jacobson phase layered perovskite HLaNb2O7 (HLN), its organic derivate propoxyl-HLaNb2O7 (pHLN), Ruddlesden-Popper phase perovskite H2SrTa2O7 (HSTO) and Aurivillius phase perovskite H2W2O7 (HWO) were synthesized and functionalized with gold NPs by in-situ methods. Gold NPs were prepared by both an aqueous method and two-phase method. The size of NPs can be adjusted by different reaction times. Overall, the latter method shows a narrower size distribution and better dispersion. In addition, most gold NPs prepared by the two-phase method were attached on the surface of nanosheets and almost no free gold NPs were observed in solution. This approach should be applicable to most layered perovskites. The aqueous and two-phase methods were also applied on the preparation of gold NPs onto H4Nb6O17 nanosheets and nanoscrolls. H4Nb6O17 nanosheets were prepared by two approaches and showed similar gold NPs attachment. LiNbO3 nanocrystals can be also modified with gold NPs by the two-phase method though free gold NPs were observed. Further studies involved the functionalization of layered perovskites and related compounds with magnetic NPs. Iron oxide and cobalt NPs were synthesized in the presence of layered perovskite and modified perovskite nanosheets were obtained.

<p>Recent advances in nanotechnology have led to the application of nanoparticles in a wide variety of fields. In the field of nanomedicine, there is great emphasis on combining diagnostic and therapeutic modalities into a single nanoparticle construct (theranostics). In particular, anisotropic nanoparticles have shown great potential for surface-enhanced Raman scattering (SERS) detection due to their unique optical properties. Gold nanostars are a type of anisotropic nanoparticle with one of the highest SERS enhancement factors in a non-aggregated state. By utilizing the distinct characteristics of gold nanostars, new plasmonic materials for diagnostics, therapy, and sensing can be synthesized. The work described herein is divided into two main themes. The first half presents a novel, theranostic nanoplatform that can be used for both SERS detection and photodynamic therapy (PDT). The second half involves the rational design of silver-coated gold nanostars for increasing SERS signal intensity and improving reproducibility and quantification in SERS measurements. </p><p>The theranostic nanoplatforms consist of Raman-labeled gold nanostars coated with a silica shell. Photosensitizer molecules for PDT can be loaded into the silica matrix, while retaining the SERS signal of the gold nanostar core. SERS detection and PDT are performed at different wavelengths, so there is no interference between the diagnostic and therapeutic modalities. Singlet oxygen generation (a measure of PDT effectiveness) was demonstrated from the drug-loaded nanocomposites. In vitro testing with breast cancer cells showed that the nanoplatform could be successfully used for PDT. When further conjugating the nanoplatform with a cell-penetrating peptide (CPP), efficacy of both SERS detection and PDT is enhanced. </p><p>The rational design of plasmonic nanoparticles for SERS sensing involved the synthesis of silver-coated gold nanostars. Investigation of the silver coating process revealed that preservation of the gold nanostar tips was necessary to achieve the increased SERS intensity. At the optimal amount of silver coating, the SERS intensity is increased by over an order of magnitude. It was determined that a majority of the increased SERS signal can be attributed to reducing the inner filter effect, as the silver coating process moves the extinction of the particles far away from the laser excitation line. To improve reproducibility and quantitative SERS detection, an internal standard was incorporated into the particles. By embedding a small-molecule dye between the gold and silver surfaces, SERS signal was obtained both from the internal dye and external analyte on the particle surface. By normalizing the external analyte signal to the internal reference signal, reproducibility and quantitative analysis are improved in a variety of experimental conditions.</p> / Dissertation

Rendre possible l'administration orale du docétaxel (Dtx), un puissant agent anticancéreux administré par voie intraveineuse, représente un défi important en cancérologie. Disposer de formulations administrables par voie orale, moins toxiques et mieux tolérées, représenterait une avancée majeure au plan clinique. Toutefois, plusieurs études ont montré que la très faible biodisponibilité du Dtx par voie orale résulte simultanément de : (i) sa faible solubilité aqueuse, (ii) son faible passage transépithélial au niveau intestinal, (iii) son efflux par les pompes d’efflux (P-gp) et son métabolisme par le cytochrome P450. Nous avons conçu une formulation capable de répondre simultanément à ces différents problèmes. Ainsi, nous avons tout d’abord fait appel aux cyclodextrines (CDs) pour augmenter la solubilité apparente du Dtx. La complexation du Dtx avec la méthyl-β-CD a permis d’augmenter la solubilité apparente du Dtx d’environ 5000 fois. Ce complexe a ensuite été associé à des nanoparticules(NPs) polymères composées d’un coeur de poly(cyanoacrylate d’alkyle) et recouvert en surface de chitosane thiolé afin de leur conférer des propriétés mucoadhésives et de diminuer localement le métabolisme. Ces NPs ont montré in vitro et ex vivo leur capacité à arriver intactes au niveau de l’intestin, d’y adhérer et de libérer le Dtx de manière contrôlée dans le temps, et finalement d’améliorer son absorption intestinale. Une évaluation de la toxicité de cette formulation vis-à-vis de la muqueuse intestinale suggère que l’encapsulation du Dtx dans les NPs assure une certaine protection de la muqueuse. Au final, la formulation orale proposée offre en perspective la possibilité de moduler la dose administrée, donc d’ajuster finement la posologie et finalement d’offrir au corps médical et aux patients les bénéfices d’une thérapie personnalisée. / Docetaxel (Dtx) is an anticancer drug widely used in therapy. However, severe allergic reactions and peripheral neurotoxicity are caused by the intravenous administration of the commercial formulation Taxotere®, requiring thus the oral administration of dexamethasone and antihistamine before infusion. In this context, there is an urgent need to design new orally administered Dtx formulations to reduce these side effects and improve the patient’s qualityof life. Dtx belongs to the Class IV of the Biopharmaceutical Classification System, which comprises substances with both low solubility in aqueous fluids and low apparent intestinal permeability. This represents a major drawback when foreseeing oral delivery. Moreover, Dtx has been shown to be substrate of biological transporters and/or metabolized in the intestinal barrier. We designed a formulation able to overcome these different problems. First of all, we solved the low solubility problem by using cyclodextrin (CDs). The complexation of Dtx with the Methyl-ß-CD allowed increasing the apparent solubility of the Dtx about 5000 times. This complex was then associated to polymeric core-shell nanoparticles (NPs) based on poly(isobutyl cyanoacrylate) coated with thiolated chitosan. Among the characteristics of this system, mucoadhesion properties are the most important for an oral administration. The presence of the positively charged chitosan chains, and the thiol groups at the surface allow NPs to adhere to the mucus layer. In vitro and ex vivo experiments showed that these NPs were able to ensure a time-controlled release of Dtx and to improve its absorption at the intestinal level. An evaluation of the local intestinal toxicity of this formulation suggests that the encapsulation of Dtx into polymeric NPs had a protective effect allowing a preservation of the mucosa integrity. The further step will be to confirm by in vivo studies if this kind of nanoparticles is able to enhance the bioavailability of Dtx allowing to display an anti-tumor activity.

Atualmente, nanopartículas (NPs) são utilizadas em todos os ramos da tecnologia. Suas promissoras aplicações envolvem entre outros, o campo dos sensores e transdutores, mídia de gravação magnética, carreadores magnéticos de drogas medicinais. Com o objetivo de produzir NPs pelo método físico, um gerador de nanopartículas foi adaptado usando um dos canhões do sistema de magnetron sputtering, baseando-se no método de agregação gasosa. Com o gerador somos capazes de produzir NPs de diversos materiais e codepositá-las em matrizes dielétricas ou metálicas. Neste trabalho apresentamos o desenvolvimento da metodologia para a produção de nanopartículas de materiais magnéticos duros, usando alvos de SmCo5, Sm2Co17, Nd2Fe17B, FePt e CoPt. Investigamos a influência dos parâmetros de deposição (pressão, fluxo de gás e potência de sputtering), tipo de substrato e a existência de buffer e/ou codeposição, na obtenção das propriedades estruturais e magnéticas desejadas para esses materiais. As NPs produzidas são analisadas magneticamente pelo VSM e SQUID, sua morfologia e tamanho por TEM e SEM, a sua estequiometria pelo RBS, e a sua estrutura cristalina por XRD, a fim de obter nano-ímãs de alta anisotropia magnética. Da caracterização morfológica, através de microscopia eletrônica, encontramos para as NPs produzidas e estudadas diâmetros entre 5 e 17 nm. Através de análises de RBS obtemos para composição das NPs que as mesmas possuem estequiometria diferente dos alvos usados. Estudos estruturais e magnéticos mostram que para Sm-Co, Fe-Pt e Co-Pt é possível obter NPs cristalinas e com coercividade da ordem de 1 kOe. / In the recent years, nanoparticles (NPs) are being in all fields of technology. Their promising applications involve among others, the field of sensors and transducers, magnetic recording media, magnetic carriers of medicinal drugs. Aiming to produce NPs by physical method, a generator of nanoparticles was adapted using a system of guns \"magnetron sputtering\", based on the aggregation gas method. With the generator we are able to produce NPs with different types of material. In this work, we present the development of the methodology for the production of nanoparticles of hard magnetic materials, using targets of SmCo5, Sm2Co17, Nd2Fe17B, FePt and CoPt. We investigated the influence of the deposition parameters (pressure, gas flux and sputtering power), substrate type and the existence of the buffer and/or codeposition layers, to obtain the desired structural and magnetic properties for the nanoparticles. The produced NPs were magnetically analyzed by VSM and SQUID, the morphology and size by TEM and SEM, the stoichiometry by RBS and the crystal structure by XRD. The main objective of this work is to obtain nano-magnet with high magnetic anisotropy. Through the morphological characterization by electron microscopy, we found for NPs produced and studied have diameters between 5 and 17 nm. Through RBS analysis we have obtained the composition of the NPs, and also that they have different stoichiometry in relation to the used targets. Structural and magnetic studies have show that for Sm-Co, Fe-Pt and Co-Pt it is possible to obtain crystalline NPs with coercive field around 1 kOe.

A tecnologia de nanocompósitos é aplicável a uma vasta gama de polímeros termoplásticos e termofixos. A utilização de subprodutos da cana de açúcar tem sido extensivamente estudada como fonte de reforços para os nanocompósitos. O bagaço da cana é largamente utilizado na cogeração de energia e, como resultado da queima deste material, são produzidas milhões de toneladas de cinzas. Para este trabalho, sílica contida nas cinzas do bagaço da cana de açúcar foi extraída por método químico e método térmico. O método térmico se mostrou mais eficiente levando a uma pureza de mais de 93 % em sílica, enquanto o método químico gerou sílica bastante contaminada com cloro e sódio provenientes dos reagentes da extração. As partículas de sílica obtidas foram avaliadas por espalhamento de luz dinâmico (DSL) e apresentaram tamanho médio de 12 &mu;m. Estas partículas foram submetidas à moagem em moinho de bolas e na sequência a tratamento sonoquímico em meio líquido. As partículas de sílica tratadas no processo sonoquímico a 20 kHz, potência de 500 W e 90 minutos tiveram suas dimensões reduzidas a escala nanométrica da ordem de dezenas de nanômetros. A nanossílica obtida foi então incorporada como reforço em polietileno de alta densidade (HDPE). Ensaios mecânicos e termo-mecânicos mostram ganhos de propriedades mecânicas, com exceção da propriedade de resistência ao impacto. O ensaio de deflexão térmica (HDT) mostrou que a incorporação deste reforço no HDPE levou a um pequeno aumento nesta propriedade relação ao HDPE puro. A cristalinidade dos nanocompósitos gerados foi avaliada por meio de calorimetria exploratória diferencial (DSC) e observou-se um decréscimo de cristalinidade do material quando a incorporação de reforço foi de 3%. O material irradiado a 250 kGy com feixe de elétrons mostra ganhos acentuados na principais propriedades do mesmo, principalmente devido ao alto nível de reticulação do HDPE irradiado. / The nanocomposite technology is applicable to a wide range of thermoplastic and thermoset polymers. The use of sugar cane byproducts has been extensively studied as a source of reinforcement for nanocomposites. The bagasse is widely used in cogeneration and as a result of the burning of this material, millions of tons of ash are produced. For this work, silica contained in the ashes of bagasse from sugarcane was extracted by chemical method and thermal method. The thermal method is more efficient leading to a purity of more than 93% of silica, while the chemical method generated silica contaminated with chlorine and sodium from the extraction reagents. The silica particles obtained were evaluated by dynamic light scattering (DSL) and presented an average size of 12 micrometers. These particles were submitted to grinding in a ball mill and then to a sonochemical treatment. Silica particles treated by the sonochemical process ( 20 kHz, 500 W and 90 minutes) had its dimensions reduced to nanometric scale of tenths of nanometers. The nanossílica obtained was then used as reinforcement in high density polyethylene (HDPE). Mechanical and thermo-mechanical properties were assessed and gains were shown for mechanical properties , except for the impact resistance. The distortion temperature (HDT) showed that the incorporation of the reinforcement in HDPE led to a small increase in this property compared to pure HDPE. The crystallinity of the nanocomposites generated was evaluated by differential scanning calorimetry (DSC) and it was observed a decrease of crystallinity in the material when the reinforcing incorporation was 3%. The material irradiated to 250 kGy with electron beam showed important property gains, mainly due to the high level of crosslinking of irradiated HDPE.

The objective of this research was to study the adsorption and photodegradation of crystal violet (CV) dye by using poly(2-hydroxyethylmethacrylate) (PHEMA) hydrogel and nanocomposite TiO2-PHEMA hydrogel. Since the TiO2 nanoparticle has poor solubility, another goal of this study was to make a uniform TiO2 nanocomposite gel. These gels can be used in water treatment and can be easily photodegrade by exposure of sunlight which is similar to exposing to UV-vis. PHEMA was synthesized by free radical polymerization. The nanocomposite gels were characterized by FT-IR and XRD to confirm the presence of TiO2 nanoparticles and CV dye inside the PHEMA hydrogel. The XRD data showed that not only maintaining the crystallinity of the three different phases that had been used, but also the uptake of the dye inside the nanocomposite gels. Moreover, the FT-IR demonstrated the presence of the functional groups of the chemical structure of the gel as well as the nanocomposite gels with the CV dye. The adsorption of CV dye was examined through monitoring UV-Vis absorption. The kinetic study indicated the adsorption of the dye by the nanocomposite gels until reached equilibrium, which is the zero concentration. The photodegradation of CV dye was examined using a medium pressure Hg lamp. It was determined that the composite gels adsorb CV dye from the solution at the beginning while under the photochemical condition. Eventually, the dye in the gel was photodegraded, indicating that in the gel system, the photodegradation process is still effective to dyes. The composite gels containing pure anatase phase titanium are much better photocatalysts and took less time of adsorption than those containing pure rutile and anatase/rutile mixed phases of titania.

<div>Nanoparticles (NPs) are an emerging technology in biomedical engineering with opportunities in diagnostics, imaging, and drug delivery. NPs can be prepared from a wide range of organic and/or inorganic materials. They can be fabricated to exhibit different characteristics for biomedical applications. The goal of this thesis was to develop NPs with tunable surface properties for selective cell targeting. Specifically, polyelectrolyte complexes composed of heparin (Hep, a growth factor binding glycosaminoglycan) and poly-L-lysine (PLL, a homopolymeric lysine) were prepared via a pulse sonication method. The Hep/PLL core NPs were further layered with additional Hep, tetrazine (Tz) modified Hep, or dextran sulfate (DS). The addition of Tz handle on Hep backbone permitted easy modification of NP surface with norbornene (NB) modified motifs/ligands, including inert poly(ethylene glycol) (PEG), cell adhesive peptides (e.g., RGD), and/or fluorescent marker. Both Hep and DS coated NPs could be readily internalized by J774A.1 monocytes/macrophages, whereas PEGylated NPs effectively reduced cellular uptake/recognition. The versatility of this NP system was further demonstrated by laying DS on the Hep/PLL NP surface. DS-coated NPs were recognized by J774A.1 cells more effectively. Furthermore, DS-layered NPs seemed to reduce IL-10 production on a per cell basis, suggesting that these NPs could be used to alter polarization of macrophages.</div>

A nanoemulsão LDE tem composição lipídica semelhante à da LDL natural e é utilizada para estudos do metabolismo da LDL. Estudos anteriores mostraram que a LDE é captada pelas células pelo LDL-r, porém outros receptores podem estar envolvidos nesta captação, como LRP-1, CD36 e CD68. Os objetivos deste estudo foram: investigar a captação da LDE por células endoteliais, fibroblastos, monócitos, macrófagos e H292, identificar os receptores envolvidos na captação da LDE pelas mesmas células e avaliar os efeitos da modificação química da LDE sobre a estabilidade, captação celular, lipoperoxidação celular e citotoxicidade. A LDE marcada com [3H]-colesterol livre e [14C]-éster de colesterol foi incubada por 4 horas com as linhagens celulares. Após a incubação, foram realizados os testes de captação da LDE e competição da LDE com a LDL natural. A expressão dos receptores LDL-r, LRP, CD36 e CD68 foi avaliada pelos métodos de imunocitoquímica, citometria de fluxo e PCR real time. Para investigar os efeitos da modificação da LDE (LDE-CO), o éster de colesterololeato de colesterol (monoinsaturado), foi substituído por linoleato de colesterol (LDE-CL) (poliinsaturado) e por estearato de colesterol (LDE-CE) (saturado). Estas nanoemulsões foram submetidas a testes de estabilidade (tamanho, polidispersão, pH e peroxidação), captação celular, peroxidação lipídica celular e citotoxicidade. Nos resultados, foi observado que todas as células estudadas internalizaram o colesterol livre e éster de colesterol proporcionalmente às concentrações de LDE-CO incubadas com diferença de saturação entre elas, sendo o colesterol livre mais captado que o éster de colesterol da LDE-CO por todas as células estudadas. Além disso, os monócitos (THP-1) demonstraram maior captação de LDE-CO que as demais células. No estudo de competição com a LDL natural ocorreu uma diminuição da captação (r2-0,73), sugerindo que as duas partículas competem pelo mesmo receptor. A LDE-CO foi capaz de inibir a expressão protéica dos receptores LDL em HUVEC (3,98 vezes), monócito (6,25 vezes) e fibroblasto (3,70 vezes) e a expressão gênica em monócito e HUVEC. Por citometria de fluxo, a expressão protéica do LDL-r em H292 e fibroblasto diminuiu. Em HUVEC a LDE-CO aumentou a expressão protéica em 3,57 vezes, já em monócito, a LDE-CO diminuiu a expressão gênica e protéica (3,15 vezes) do LRP-1. Em macrófago e em H292, a LDE-CO aumentou a expressão gênica do LRP-1. A LDE-CO foi capaz de aumentar a expressão gênica e protéica (3,1 vezes) do CD36 em HUVEC, diminuir a expressão protéica (4,34 vezes) em macrófago e diminuir a expressão gênica e protéica (2,94 vezes) em H292. A LDE foi capaz de aumentar a expressão protéica (2,09 vezes) do CD68 em H292, e aumentar a expressão gênica em monócito e macrófago. A linhagem celular que apresentou maior taxa de sobrevivência na presença da LDE-CO foi o fibroblasto. Nas análises dos efeitos da modificação química da LDE, a LDE-oleato apresentou o tamanho e a lipoperoxidação menores que a LDE-linoleato e LDE-estearato. Nenhuma das LDEs apresentou modificação da estabilidade antes de 30 dias. As células apresentaram maior lipoperoxidação na presença de LDECL quando comparada à presença de LDE-CO e LDE-CE. A captação de [3H]-colesterol livre foi maior que de éster de colesterol das três LDEs por todas as células estudadas. A composição da LDE com oleato de colesterol foi a que apresentou características mais favoráveis em termos de tamanho de partículas e susceptibilidade à peroxidação. A captação celular do colesterol livre foi maior do que a do éster de colesterol em todas as linhagens estudadas das três LDEs, sugerindo que o colesterol livre possa dissociar-se da LDE e ser captado pelas células por vias não específicas. Os dados obtidos neste trabalho ajudam na compreensão dos mecanismos de captação e da influência da composição na estabilidade e adequação do sistema LDE e outros similares às suas potenciais aplicações terapêuticas ou diagnósticas. / With fat composition similar to natural LDL, the LDE nanoemulsion can be used to study the metabolism of LDL. Other studies have shown that LDE is uptaken by cells by LDL-r receptors. Other receptors such as LRP-1, CD36 and CD38 may also be involved in the uptake. The objectives of this study were to investigate the uptake of LDE by endothelial and tumor cells, fibroblasts, monocytes and macrophages, to identify those receptors involved in this process and to evaluate the effects on LDE uptake by changing its chemical composition. A labeled LDE with [3H]-cholesterol and [14C]- cholesteryl ester was incubated for 4 hours with cells, after which LDE uptake and competition tests were evaluated. LDL-r, LRP, CD36 and CD38 were evaluated by using immunocytochemistry methods, cytometric flow and real time PCR. To investigate the effects of LDE chemical composition modifications, cholesteryl oleate (LDE-CO) was replaced with cholesteryl linoleate (LDE-CL) and cholesterol stearate (LDE-CE). These were then tested for stability, cellular uptake, lipoperoxidation and citotoxitity. Results showed that all cells internalized [3H]-cholesterol and [14C]-cholesteryl ester proportionally to incubated LDE-CO concentrations albeit with some saturation differences. LDE-CO lipid uptake had a higher cholesterol uptake than the cholesteryl ester uptake. Furthermore, monocytes (THP-1) had a higher LDE-CO uptake than other cells. LDE-CO uptake decreased (r2 -0.73) in the presence of natural LDL, suggesting that these two particles may be competing for the same receptors. LDE-CO appeared to inhibit LDL protein receptor expression in HUVEC (3.98 times), in monocytes (6.25 times) and in fibroblasts (3.70 times), as well as the gene expression in monocytes and HUVEC. A decrease in LDL-r expression in both H292 and fibroblasts was also observed. LDE-CO increased the protein expression in HUVEC 3.75 times while in monocytes, it was able to decrease gene and protein expression of LRP-1, 3.15 times. In macrophages and H292, there was an increase in genetic expression of LRP-1. LDE-CO increased the CD36 in HUVEC gene and protein expressions 3.1 times, decreased the macrophage protein expression 4.34 times and decreased the H292 gene and protein expression 2.94 times. LDE increased protein expression 2.09 times in CD68 in H292 and increase gene expression in both monocytes and macrophages. Fibroblasts presented the highest survival rate in the presence of LDE-CO of all cells studied. The LDE chemical modification effect studies, presented smaller sized LDE-CO and less lipoperoxidation than LDE-CL and LDE-CE presented no stability modifications in less than 30 days. Cells presented higher lipoperoxidation in the presence of LDE-CL when compared to the presence of LDE-CO and LDE-CE. [3H]-cholesterol was greater than cholesteryl ester for all three LDE types in all the studied cells. LDE-CO presented favorable characteristics in terms of particle size and susceptibility to peroxidation. Cholesterol cell uptake was higher than that of cholesteryl ester for all LDEs of all the studied cells which suggests that that cholesterol may be capable of disassociating itself from LDE and being uptaken by cells through non-specific pathways. The results of this study can help to better understand the mechanisms of uptake by cells, the effects of stability and LDE system adequation for therapeutic and diagnostic applications.

Neste trabalho descreve-se o estudo das reações de oxidação eletroquímica de metanol e etanol em catalisadores contendo platina (Pt) e Nióbio (Nb) suportados em carbono de alta área superficial. Os materiais estudados foram PtNb/C, Pt-Nb2O5(amorfo)/C e Pt-Nb2O5(cristalino) /C, utilizando-se como padrão para comparação o catalisador comercial Pt/C E-TEK 20 %. A caracterização física foi realizada com o auxílio das técnicas de Difração de Raios X (DRX), Espectroscopia por Energia Dispersiva de Raios X (EDX) e Espectroscopia de Absorção de Raios X (XAS). A partir dos picos de difração foi possível calcular o tamanho médio de cristalito e o parâmetro de rede das amostras estudadas. Os espectros de XAS na região de XANES sugerem que a Pt suportada sobre os óxidos de nióbio tem uma menor tendência a sofrer perda de densidade eletrônica na banda 5d. O comportamento eletroquímico dos catalisadores frente às reações de eletro-oxidação dos alcoóis foi avaliado através de voltametrias de varredura linear, voltametrias cíclicas e cronoamperometrias com o eletrodo de trabalho preparado com uma configuração de camada ultrafina. Os dois catalisadores contendo Pt suportada sobre os óxidos de nióbio apresentaram os melhores desempenhos na oxidação eletroquímica dos alcoóis, no entanto os três materiais estudados deslocaram o pico de oxidação de CO (ads) para menores valores de potencial em relação à Pt/C E-TEK 20 %. Experimentos de Espectroscopia de absorção na região do Infravermelho in situ com Transformada de Fourier (FTIR) foram realizados com o intuito de se identificar os adsorbatos formados durante a eletro-oxidação de etanol. A presença dos óxidos de nióbio não favorece significativamente à conversão de etanol a CO2, sendo os principais produtos da oxidação o acetaldeído e o ácido acético. Por fim foram realizados testes na célula a combustível unitária seguindo-se a mesma abordagem que nos estudos de camada ultrafina. / In this work, the methanol and ethanol electrochemical oxidation reactions are studied on platinum (Pt) and niobium (Nb) catalysts supported on high surface area carbon. The selected materials were PtNb/C, Pt-Nb2O5(amorphous) /C e Pt-Nb2O5(crystalline) /C, using as reference for comparison purposes the commercial catalyst 20% Pt-C E-TEK. The catalysts were physically characterized by X-Ray Diffraction (XRD), Energy-dispersive X-ray spectroscopy (EDS) and X-ray Absorption Spectroscopy (XAS). The average crystal size and lattice parameters of the studied materials were assessed from the diffraction peaks. XAS spectra in the XANES region indicated that the supported platinum on the niobium oxide possesses a lower tendency to lose electronic density from the 5d band. The electrochemical performance of the different catalysts was evaluated by linear sweep voltammetry, cyclic voltammetry and chronoamperometry, using an ultra-thin layer electrode. The two catalysts containing platinum supported on the niobium oxide showed the best performances for the electrochemical oxidation of the alcohols, though the three studied materials displaced the CO (ads) oxidation peak for lower potential values compared to 20% E-TEK Pt/C. In situ Fourier Transform Infrared Absorption Spectroscopy (FTIR) experiments were carried out in order to identify the formed adsorbates during the ethanol electroxidation. The presence of the niobium oxides does not significantly favour the conversion of ethanol to CO2, being the main products of the oxidation acetaldehyde and acetic acid. Finally, fuel cell tests were carried out following the same procedure as in the case of the ultra-thin layer.