Thesis (Ph.D.) - University of St Andrews, March 2008.

Thesis (Ph. D.)--University of Texas at Austin, 2006. / Vita. Includes bibliographical references.

Thesis (Ph.D.)--Ohio University, June, 2008. / Abstract only has been uploaded to OhioLINK. Includes bibliographical references (leaves 199-209)

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Malgré ces propriétés intéressantes et l'abondance du matériau brut dont on peut les extraire, les applications des CNC pour des produits commerciaux restent limitées en raison des limitations liées à l’utilisation de procédés industriels. En effet, les matériaux produits à base de CNC sont généralement préparés par la technique de coulée/évaporation. Ce procédé permet de bien contrôler les propriétés comme l’humidité, la dispersion des particules et aussi d’assurer la formation d'un réseau tridimensionnel des particules. Cependant, ce procédé n'est pas facilement transposable à l'industrie. Une alternative à la technique de coulée/évaporation serait l'application du procédé d'extrusion et/ou de moulage par injection. Ces n'utilisent pas de solvants et peuvent donc être considérés comme des procédés plus verts que la coulée/évaporation. Il y a cependant des points négatifs. Ils sont essentiellement associés à des problèmes de dispersion, de dégradation thermique et de propriétés mécaniques plus faibles. Dans ce contexte, la thèse développée ici présente quelques études qui cherchent à combler quelque unes des lacunes décrites ci-dessus.Le Chapitre 1 présente une revue de la littérature et des concepts de base utilisés pendant la thèse. Dans le Chapitre 2, les particules de caoutchouc présentes dans la suspension de latex ont été oxydées en surface par addition de KMnO4 en conditions contrôlées. L’objectif était d’induire l’oxydation des doubles liaisons présentes dans la structure du caoutchouc naturel (NR). Les essais de traction cycliques ont montré que pour ces échantillons, les interactions interfaciales entre les nanoparticules et le polymère sont plus fortes. Cependant, quand le taux d’oxydation augmente, l’hydrophilie des chaînes de caoutchouc est observable.Dans le Chapitre 3, des composites à base de polycarbonate (PC) et de CNC ont été obtenus par la technique d’extrusion. Ce procédé implique de hautes températures (200oC) et la dégradation thermique devient alors un problème pendant la préparation des matériaux. Pour limiter cette dégradation, un mélange maître (masterbatch) contenant environ 30% de CNC a été produit et utilisé comme base pour la préparation des films. La dispersion des CNC entre les chaînes de PC permet probablement d’éviter la dégradation en raison de la protection physique des nanoparticules. Malheureusement, la présence des CNC semble réduire la stabilité thermique du polymère et accélérer sa dépolymérisation. Le chapitre 4 est dédié aux systèmes à base de polybutyrate-adipate-téréphtalate (PBAT) et de nanocristaux de cellulose. Le chapitre est divisé en deux parties. La première partie est focalisée sur l’influence de la cristallisation que les nanocristaux peuvent induire sur la matrice polymère après le processus d’extrusion. Trois sources différentes de CNC ont été choisies pour permettre l’obtention de nanoparticules avec différents facteurs de forme L/d. Des nanocomposites ont été préparés par extrusion en utilisant un taux de particules correspondant au seuil de percolation. Cela a créé une sorte de compétition entre la taille de la particule et sa fraction volumique. Dans cette étude, les nanocristaux avec plus grand rapport longueur/diamètre et sont, également, responsables de la cristallisation la plus significative.Dans la deuxième partie, des nanocomposites ont également été préparés par extrusion/injection puis caractérisés en termes d’organisation structurale. Les résultats de SAOS ont montré un changement de viscosité et de la valeur de G’, ainsi que dans la pente de la courbe G’ x ω, suggérant une modification de la structure des particules après conditionnement. Grâce à les tests de rheologie 2D, il a été possible d’observer une modification de la structure des particules qui suggère une plus grande dispersion. Cependant, il est clair que les particules ne sont pas complètement réorganisées sous forme de réseau 3D. / The preparation of composites based on cellulose nanocrystals (CNC) is normally performed using techniques such as melt processing or casting/evaporation. In the last one, impressive mechanical properties can be reached due to the creation of a particle 3D network that is based on new hydrogen bonds between the cellulose nanorods. This process of new H-bond formation normally takes time and is dependent of the nanoparticle size and its volume fraction. Besides, the quality of filler dispersion into the polymeric matrix is also an important parameter to provide the highest surface area and provides an ideal structure for the rigid structure. In this work, we tried to propose different preparation methods and characterizations to obtain nanocomposites with a simple preparation either by casting/evaporation or melt processing.First, we improve the compatibility between an hydrophobic matrix and CNC by the chemical modification of the former. This approach tried to be an alternative to standard modification process, normally performed on nanoparticle surface by –OH groups substitution. As a good model for the study of composite mechanical properties, a natural rubber matrix was used with double bonds oxidized by the use of a strong oxidant aiming to introduce new hydroxyl groups on the isoprene chains. These new groups seem to interact with the cellulose surface, creating new supramolecular interactions between particle and matrix. It was observed that the increase in the degree of oxidation can first increase the compatibility between the polymer and the filler, increasing the mechanical properties. Later, over-oxidation starts to cause the plasticization of the system.In sequence, we had use melt processing for produce nanocomposites at high temperatures by using amorphous and semi-crystalline polymers. In a first approach, CNC were coated with the matrix polymer (polycarbonate) by a system of dilution/precipitation in suitable solvents. The coated nanocrystals are extruded with polycarbonate at 230ºC thanks to the coating approach, that allows an increase in the processing temperature of CNCs. Also, this technique improves its dispersion in the matrix due to entanglement of the polymer chains and the individual nanocrystals. The thermal analyzes shows that the CNC presence and coating masterbatch preparation reduces the polycarbonate Activation Energy (Ea) causing an acceleration in its thermal degradation and a molecular weight (Mv) reduction. As consequence, an increase in the crystallinity of the material occurs. Mechanical characterizations (DMA) show that nanocrystals presence and Mv reduction incresed the mechanical properties of the materials. The modulus (E') values, after the Tg, are higher than theoretical values calculated by Halpin−Kardos model for all studied compositions.The last part of this work is focused on investigate the influence of extrusion and thermal history of the material on its mechanical and rheological properties.In a first approach, we investigated the role of CNCs with different sizes on the material’s final properties (i.e. crystallinity and mechanical properties). Different sources were used to obtain CNCs with different percolation volume fractions, aiming to investigate its capacity on crystallization of a semi crystalline thermoplastic matrix. The results showed that crystallinity and mechanical properties are, indeed, strongly affected by the aspect ratio of the nanorod. In fact, longer CNC particles seem to be more capable to create crystalline domains and reinforce the polymer despite the lower total number of particles. In a second step, the rheological properties of the materials were investigated to characterize the effect of particle micro-structure. The composite internal organization seems to be dependent of the system viscosity and filler volume fraction, what can bring strong impact on the mechanical properties of the material.

La médecine moderne fait aujourd’hui face à de nombreux défis, comme le diagnostic précis et rapide des maladies. En raison de leurs propriétés photophysiques uniques, les quantum dots (QDs) sont des marqueurs fluorescents prometteurs pour la détection biologique. Le but principal de ce travail est le développement de conjuguées QD-anticorps (AB) en vue de leur utilisation dans des fluoroimmunoassays FRET (Förster Resonance Energy Transfer) pour la détection de la PSA (Antigène Spécifique de la Prostate), biomarqueur du cancer de la prostate. Dans ces systèmes, les QDs agissent comme accepteurs d’énergie en combinaison avec des complexes de terbium agissant comme donneurs. Grâce aux propriétés de luminescence spécifiques de ces deux classes de fluorophores, la mesure résolue en temps du signal de QDs permet la détection rapide et sensible des marqueurs biologiques. Nous avons développé une nouvelle approche en deux étapes pour la fonctionnalisation et la bioconjugaison de QDs qui donne des systèmes QD-AB fortement luminescents, stables et ultra compacts, maximisant ainsi l'efficacité de FRET. Dans une première étape, le transfert en phase aqueuse de QDs de phosphure d’indium (InP) synthétisés au laboratoire, émettant à 530 nm et de QDs commerciaux de CdSe émettant à 605 nm et 705 nm a été réalisé par échange de ligands de surface avec de la pénicillamine. Ensuite, la post-fonctionnalisation avec un ligand hétérobifonctionnel contenant un groupe acide lipoïque et une fonction maléimide permet le couplage ultérieur à des groupes sulfhydryle des protéines, a été effectuée. Après conjugaison des QDs avec des anticorps fragmentés (F(ab)) un très petit diamètre hydrodynamique (<13 nm) et une stabilité colloïdale à long terme (plusieurs années) ont été obtenus. L'applicabilité des sondes obtenues a été confirmée par la détection de PSA dans des échantillons de sérum, avec des limites de détection (LOD) très basses (0,8 ng/mL) pour les sondes émettant à 705 nm, dont l'absorption du spectre montre le plus grand recouvrement spectral avec l'émission du Tb. De plus, le greffage direct de complexes de terres rares sur la surface de QD a également été exploré, donnant accès à des sondes bimodales pour l'imagerie par resonance magnétique et par fluorescence (avec Gd) ou à des sondes biluminescentes (avec Eu, Yb). Dans ce dernier cas, la sensibilisation de la luminescence proche infrarouge de l’Yb par les QDs à base d’InP a été démontrée. Enfin nous avons réalisé des études de nanotoxicologie sur les différents types de QDs utilisés. En particulier, nous avons étudié la toxicité in vivo en utilisant l'organisme modèle Hydra vulgaris et la toxicité in vitro en utilisant des cellules de kératinocytes humains en comparant l’effet de systèmes cœur et cœur-coquille de QDs d’InP et de CdSe. / One of the many challenges modern medicine is facing today is the accurate and early diagnosis of diseases. Due to their unique photophysical properties semiconductor quantum dots (QDs) are promising fluorescent labels for biosensing. The major aim of this work is the development of QD antibody (AB) conjugates to be used in Förster resonance energy transfer (FRET) immunoassays for the detection of the tumor biomarker PSA (prostate specific antigen). In these assays, the QDs act as FRET acceptors in combination with terbium complex donors. Thanks to the specific luminescence properties of these two classes of fluorophores, time-gated detection of the QD signal allows for the fast and sensitive detection of biomarkers. We developed a novel two-step approach for QD functionalization and bioconjugation which yields ultra compact, stable and highly luminescent QD-AB conjugates maximizing FRET efficiency. In the first step aqueous phase transfer of lab-synthesized InP-based QDs emitting at 530 nm and of commercial CdSe-based QDs emitting at 605 nm and 705nm was achieved by surface ligand exchange with penicillamine. Then, post-functionalization with a heterobifunctional crosslinker, containing a lipoic acid group and a maleimide function, enabled the subsequent coupling to sulfhydryl groups of proteins. This was demonstrated by QD conjugation with fragmented antibodies (F(ab)); the obtained conjugates have a very low hydrodynamic diameter < 13 nm and long-term colloidal stability. The applicability of the obtained probes was confirmed by the detection of PSA in serum samples with detection limits (LODs) down to 0.8 ng/mL for the 705 nm emitting probes, whose absorption spectrum shows the largest overlap integral with the Tb emission. In addition, direct grafting of rare earth complexes on the QD surface has also been explored, giving access to dual-mode imaging agents (with Gd) or to biluminescent (with Eu, Yb) probes. In the latter case, the sensitization of Yb NIR luminescence by InP-based QDs has been firstly demonstrated. Finally, we carried out nanotoxicological studies on the different types of QDs used. In particular we investigated in vivo toxicity using the model organism Hydra Vulgaris and in vitro toxicity using human keratinocyte cells comparing core and core/shell InP-based and CdSe-based QDs.

Depuis une dizaine d'années, les nanofibres et nanocristaux organiques fluorescents font l'objet d'un intérêt croissant. On les considère de plus en plus comme des matériaux fonctionnels pour des applications dans le domaine de l'optoélectronique, des capteurs chimiques et biochimiques et de la biologie. Cela implique que l'on soit capable de fabriquer des nanofibres et des nanocristaux organiques fluorescents de bonne qualité, avec des coûts raisonnables et en quantité suffisante. Or, le développement récent de ces matériaux se heurte encore à de nombreuses limitations dont la principale est que très peu de molécules sont fluorescentes à l'état solide. En effet, il ne suffit pas que la molécule soit intrinsèquement fluorescente. Les propriétés photophysiques à l'état solide dépendent de l'arrangement moléculaire, qui est souvent défavorable à l'émission de fluorescence. De plus, peu de molécules donnent spontanément des fibres et il est difficile d'obtenir des nanocristaux de taille homogène. Heureusement, les molécules organiques se prêtent à de multiples modifications par voie de synthèse et de petits changements de structure entraînent de grandes variations dans les propriétés d'auto-association. Cela permet de jouer à la fois sur les propriétés photophysiques et sur la morphologie des particules obtenues. Nous disposons de dérivés de coumarines et d'iminocoumarines qui ont la propriété rare d'être très fluorescents à l'état solide. Certains sont même plus fluorescents à l'état solide qu'en solution. Le but de cette thèse est maintenant de développer cette série de composés, de les mettre sous forme de nanoparticules et d'étudier la relation structure/propriétés dans ces nouveaux objets en vue d'applications pratiques. Nous nous orienterons vers les applications les plus favorables (optique ou bio-imagerie médicale). En particulier, nous essaierons d'utiliser les nanocristaux pour marquer les cellules cancéreuses et mettre au point un nouveau système pour le diagnostic précoce des tumeurs. / In the last decade, fluorescent organic nanofibers and nanocrystals have been the object of an increasing interest. They are now considered as promising functional materials for applications in the fields of optoelectronics, chemical or biochemical sensors, and biology. A prerequisite for applications is the ability to produce good quality fluorescent organic nanofibers and nanocrystals, with reasonable costs and in sufficient amounts. However, the recent development of these materials is impeded by numerous limitations, the major one being that very few molecules are fluorescent in the solid state. Indeed, the photophysical properties in the solid state depend on the molecular arrangement, which is often unfavorable to fluorescence emission. Furthermore, few molecules give spontaneously fibers, and it is difficult to obtain nanocrystals of homogeneous size. Fortunately, organic molecules lend themselves well to various modifications by synthesis. Small structural changes entail big variations in both the photophysical and self-association properties. new coumarin and iminocoumarin derivatives have been designed and prepared. They exhibit the rare property to be very fluorescent in the solid state. Some are even more fluorescent in the solid state than in solution. The purpose of this thesis is now to develop this series of compounds, to put them in the form of nanoparticles and to study the structure/properties relationship in these new objects with the aim of practical applications. According to our obtained results, we shall turn to the most favorable applications (optics or bio-medical imaging). In particular, we shall try to use nanocrystals to label cancer cells with the aim to develop a new system for the early diagnosis of tumors.

VIANA NETO, Bartolomeu Cruz. Propriedades estruturais e vibracionais de nanocristais de TiO2 dispersos em matriz vítrea porosa. 2006. 49 f. Dissertação (Mestrado em Física) - Programa de Pós-Graduação em Física, Departamento de Física, Centro de Ciências, Universidade Federal do Ceará, Fortaleza, 2006. / Submitted by Edvander Pires (edvanderpires@gmail.com) on 2014-11-13T22:08:54Z No. of bitstreams: 1 2006_dis_bcviananeto.pdf: 1287691 bytes, checksum: a818652b8c5c3fe5884464f939ed254d (MD5) / Approved for entry into archive by Edvander Pires(edvanderpires@gmail.com) on 2014-11-13T22:19:20Z (GMT) No. of bitstreams: 1 2006_dis_bcviananeto.pdf: 1287691 bytes, checksum: a818652b8c5c3fe5884464f939ed254d (MD5) / Made available in DSpace on 2014-11-13T22:19:20Z (GMT). No. of bitstreams: 1 2006_dis_bcviananeto.pdf: 1287691 bytes, checksum: a818652b8c5c3fe5884464f939ed254d (MD5) Previous issue date: 2006 / Nanostructured materials are the subject of intense investigation due to their remarkable properties as compared their bulk counterparts. The size-induced phenomena are interesting their own and open unique opportunities not only for using these properties in novel applications but also for improving the current technology. In this scenario integrated chemical systems (ICS) are set apart owing their complexity and the possibility ofcombining diferent nanosystems for getting materials with a designed functionality. For instance, nanocrystal growth in the cavities of a porous host is an attractive ICS because the porous is a restricted environment that can be used as nanoreactors. Besides the such system is very promising for catalysis it also important for studying the size-induced properties of the guest material as well. In this work we report the study of vibrational and structural properties of TiO2 nanocrystals dispersed into a porous vycor glass. We have obtained very small TiO2 nanocrystals in the anatase form. The nanocrystal size is controlled via the mass increment only thus preventing the growth through the coalescence process. The nanocrystal size as monitored through transmission electron microscope and Raman scattering. The Eg lowest frequency mode experiences an upshift and becomes broader as the nanocrystal size decreases. This phenomena is attributed to a size-induced e®ect and we analyzed it based on a phonon con¯nement model. As the nanocrystal size gets smaller the q = 0 selection rule is relaxed and the phonon con¯nement involves large q values contribute to the Raman intensity. The frequency follows the same trend of the phonon dispersion relation for the TiO2 bulk as the nanocrystal size decreases. / Materiais nanoestruturados são objetos de intensa investigação devido as suas notáveis propriedades físicas e químicas e quando comparados em suas formas “bulk". Os fenômenos induzidos pela redução do tamanho são interessantes por si próprio e abrem oportunidades únicas, não somente para o uso dessas propriedades em várias aplicações más também para o aprimoramento da tecnologia corrente. Os sistemas químicos integrados (SQI) são um conjunto à parte com complexidade própria e diferentes possibilidades de combinações de nanosistemas para obtenção de materiais com uma funcionalidade desejada. Por exemplo, o crescimento de nanocristais nas cavidades de um hospedeiro poroso é um SQI atrativo, pois o ambiente dos poros pode ser usado como nanoreatores. Da mesma forma que o sistema pode ser muito promissor para catálise é também importante no estudo das propriedades induzidas pelo tamanho do material hóspede. Neste trabalho, estudamos as propriedades estruturais e vibracionais de nanocristais de TiO2 dispersos dentro dos poros do vidro vycor. Foram estudados nanocristais de TiO2 com tamanhos variando de 3-20 nm na fase anatásio. O tamanho dos nanocristais foi monitorado através de microscopia de transmissão eletrônica e espalhamento Raman. O modo Eg, com freqüência em torno de 144 cm-1, experimenta um deslocamento e alargamento de seu pico com a diminuição do tamanho do nanocristal. Este fenômeno é atribuído ao efeito induzido pelo tamanho e analisamos os resultados experimentais com base no modelo de confinamento de fônons. Quando o tamanho do nanocristal é pequeno, a regra de seleção q ≈ 0 no espalhamento Raman de primeira ordem é relaxada e fônons com grandes valores de q contribuem para a intensidade do pico Raman. A freqüência do pico Raman à medida que o tamanho diminui segue o mesmo comportamento da relação de dispersão de fônons para o TiO2 “bulk".

Made available in DSpace on 2014-06-11T19:29:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-02-27Bitstream added on 2014-06-13T20:38:21Z : No. of bitstreams: 1 santos_db_me_araiq.pdf: 1599241 bytes, checksum: 8c1cd43129c7211c6d01eb6e0839aa08 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A celulose bacteriana (CB), produzida na superfície do meio de cultura da bactéria Gluconacetobacter xylinus foi utilizada para a produção de nanocristais de celulose, ou seja, cristalitos de celulose de dimensões nanométricas isolados por meio de hidrólise ácida, que em suspensão aquosa podem se auto-organizar para a formação de fase líquido cristalina nemática quiral. Foi realizada a hidrólise ácida da CB usando ácido sulfúrico 64% (m/m) a uma temperatura de 50 °C, o tempo de hidrólise foi variado de 5 a 90 minutos e sua influência na formação dos nanocristais de celulose bacteriana (NCCB) foi avaliada. Imagens obtidas por Microscopia Eletrônica de Varredura e Microscopia de Força Atômica mostraram a formação de estruturas nanométricas semelhantes a agulhas. Medidas de Espectroscopia de Correlação de Fótons forneceram uma estimativa da variação do tamanho dos NCCB em relação ao tempo de hidrólise, que apresenta uma diminuição do tamanho até 15 minutos de reação, com populações de poucos nanômetros a 700nm, acima deste tempo não existe mudança significativa quanto a população de tamanhos. As curvas TG mostraram uma diminuição na estabilidade térmica das amostras NCCB, com início do processo de degradação cerca de 120 °C inferior ao da CB. Através da Difração de Raio-X e da equação de Segal o índice de cristalinidade da CB e dos NCCB foi calculado revelando um aumento de até dezesseis pontos percentuais na cristalinidade dos NCCB quando comparados a CB. Através da evaporação do solvente das suspensões de NCCB, filmes iridescentes foram formados. As Microscopias Óptica de Luz Polarizada dos filmes de NCCB revelaram texturas de “impressões digitais”, características dos cristais líquidos nemáticos quirais. Foram estudados a influência do tratamento de ultrassom e... / Bacterial cellulose (BC) produced from Gluconacetobacter xilinus on the surface of culture medium was used in order to produce cellulose nanocrystals, ie cellulose crystallites of nanometric dimensions isolated by acid hydrolysis, which in aqueous suspension can be self-organize to form chiral nematic liquid crystalline phase. Acid hydrolysis of BC was performed using sulfuric acid 64 % (w/w) at 50 °C. The hydrolysis time was varied from 5 to 90 minutes and its influence on the bacterial cellulose nanocrystals (BCNC) formation was evaluated. Scanning Electron Microscopy and Atomic Force Microscopy images showed the formations of nanometric needle-like structures. The Photon Correlation Spectroscopy provided an estimate of the size variation of BCNC with respect to hydrolysis time, it`s shows a decrease in size up to 15 minutes of reaction, with populations from few nanometers to 700 nm. Above this time there is no significant change in the population size. TG curves of BCNC samples revealed a decreasing on thermal stability (about 120 °C) when compared to pure BC membrane. Solid iridescent films were prepared by casting of the nanocrystals suspension. The Polarized Light Optical Microscopy revealed textures of “fingerprint”, characteristic of chiral nematic liquid crystals. The influence of the ultrasound treatment and addition of sodium chloride in the chiral nematic pitch in the reflected color of the solids films were also evaluated. The optical characterization revealed that increasing ultrasound energy increases the chiral nematic pitch... (Complete abstract click electronic access below)

Fundação de Amparo a Pesquisa do Estado de Minas Gerais / Upon the current need for research with TiO2 nanocrystals (TiO2 NCs) properly characterized in order to evaluate their biological effects, this work was done aiming to synthesize and characterize TiO2 NCs, and evaluate their biocompatibility. The nanoparticles were synthesized by the precipitation in aqueous solution technique, and characterized by the techniques of X-ray diffraction, micro-Raman and spectrophotometry. To evaluate the biocompatibility, TiO2 NCs were tested in vivo using subcutaneous implants using Balb/c mice at a dose of 1g/kg for 15, 30 and 90 days for later histological analysis of the groups of 15 and 90 days and transmission electron microscopy of the group 30 days. In vitro evaluation consisted of cell viability assays, detection and measurement of nitric oxide metabolites and measurement of cytokine production in situ and in cultured macrophages challenged with different concentrations of TiO2 NCs. Cell viability was assessed after 72 hours by the MTT colorimetric assay, using five different concentrations of a solution of 10&#956;g/ml, 20&#956;g/ml, 40&#956;g/ml, 100&#956;g/ml and 200&#956;g/ml in culture challenge of peritoneal macrophages Balb/c mice with 2, 12, 24 and 72 hours. From the supernatant of cultures of peritoneal macrophages was evaluated the production of nitrite by the Griess method and dosage levels of TNF-&#945;, IL-1&#946;, IL-12, IFN-&#61543; and IL-4 by ELISA. The same technique was used for the determination of cytokine levels obtained from subcutaneous tissues underwent implantation of TiO2 NCs. After analysis of the data distribution by Kolmogorov-Smirnov test, we proceeded to their analysis by the Kruskal-Wallis test with Bonferroni post-test. The experiments of synthesis and characterization resulted in TiO2 nanocrystals of 8.5 nm on average, mixed phase, high purity level and quantum confinement effects. Histological analysis of the 15 days group showed a intense granulomatous nonspefic type inflammatory response with signs of necrosis and hemorrhage, which progressed with a slight reduction in its intensity, observed especially at 90 days of observation. Presence of clusters of nanocrystals with macroscopic dimensions, surrounded by macrophages and multinucled giant cells forming granulomas with fibrous capsules, which could be regarded as a typical reaction of granulomatous foreign body type and more intense fibrosis formation at 90 days within the material deployed. Nanocrystals were identified in lymph nodes in the different periods of study, suggesting that these particles might be transposed. Electron microscopy confirmed the evidence of apoptosis and vacuolar degeneration. The MTT test resulted in 40% viable cells in only 10 and 20&#956;g/ml. The in vitro cytokine assay showed that there was not a tendency dose or time-dependent samples, presenting different behavior of TNF-&#945;, IL-1&#946;, IL-12 and increased production of IFN-&#61543; probably due to low production of IL -4. The nitrite production was higher in the samples of 10&#956;g/ml. The production of all cytokines in vivo experiment by the 15 days group was enhanced, decreasing in a time-dependent fashion, collaborating with the findings in vivo. We conclude that the TiO2 nanocrystals present in the tested concentrations presented inflammatory effects in vivo, cytotoxic and inflammatory conditions in vitro. These findings show that the experimental conditions studied NCs are not biocompatible. / Mediante a atual necessidade de pesquisas com nanocristais de TiO2 (NCs TiO2) devidamente caracterizados a fim de se avaliar seus efeitos biológicos, realizou-se este trabalho que teve como objetivos a síntese e caracterização dos NCs TiO2, e a avaliação de sua biocompatibilidade. As nanopartículas foram sintetizadas pela técnica da precipitação via solução aquosa, e caracterizadas por meio das técnicas de difração de raios-X, micro-Raman e espectrofotometria. Para a avaliação da biocompatibilidade, os NCs TiO2 foram submetidos a testes in vivo por meio de implantes subcutâneos utilizando camundongos Balb/c na dose de 1g/kg, por 15, 30 e 90 dias para posterior análise histológica dos grupos de 15 e 90 dias e microscopia eletrônica de transmissão do grupo de 30 dias. Avaliação in vitro consistiu de ensaios de viabilidade celular, detecção e mensuração de metabólitos do óxido nítrico e mensuração da produção de citocinas in loco e em cultura de macrófagos desafiados por diferentes concentrações de NCs TiO2. A viabilidade celular foi avaliada após 72 horas pelo teste colorimétrico MTT, utilizando-se cinco concentrações diferentes de solução de 10&#956;g/ml, 20&#956;g/ml, 40&#956;g/ml, 100&#956;g/ml e 200&#956;g/ml, em desafio de cultura de macrófagos peritoneais de camundongos Balb/c por 2, 12, 24 e 72 horas. Do sobrenadante de culturas de macrófagos peritoneais avaliou-se a produção de nitrito pelo método de Griess e dosagem dos níveis das citocinas TNF-&#945;, IL-1&#946;, IL-12, INF-&#61543; e IL-4 por ELISA. A mesma técnica foi utilizada para a dosagem dos níveis de citocinas obtida dos tecidos subcutâneo submetido ao implante de NCs TiO2. Após a análise da distribuição dos dados pelo teste Kolmogorov-Smirnov, procedeu-se a sua análise por meio do teste de Kruskal-Wallis com pós-teste de Bonferroni. Os experimentos de síntese e caracterização resultaram nanocristais de TiO2 de 8,5nm em média, fase mista, alto grau de pureza e efeitos de confinamento quântico. As análises histológicas do grupo de 15 dias evidenciaram uma resposta inflamatória do tipo granulomatosa inespecífica intensa com sinais de necrose e hemorragia, que evoluiu com discreta redução em sua intensidade, constatada em especial aos 90 dias de observação. Presença de aglomerados de nanocristais de dimensões macroscópicas, rodeados de macrófagos e células gigantes multinucleadas formando granulomas, com cápsulas fibrosas, que poderiam ser consideradas como uma reação típica do tipo granulomatosa de corpo estranho e formação de fibrose mais intensa aos 90 dias no interior do material implantado. Houve a identificação dos nanocristais nos linfonodos nos diferentes períodos de estudo, sugerindo que estas partículas possam ser carreadas a distância. A microscopia eletrônica confirmou a evidência de apoptose e degeneração vacuolar. O teste MTT resultou em 40% de células viáveis somente em 10 e 20&#956;g/ml. A dosagem de citocinas in vitro demonstrou que não houve uma tendência dose ou tempo dependente das amostras, apresentando comportamentos distintos de produção de TNF-&#945;, IL-1&#946;, IL-12 e maior produção de INF-&#61543; devido provavelmente à baixa produção de IL-4. A produção de nitrito foi maior nas amostras de 10&#956;g/ml. A produção de todas as citocinas do experimento in vivo pelo grupo de 15 dias foi acentuada, decrescendo de forma tempo dependente, colaborando com os achados in vivo. Conclui-se que os nanocristais de TiO2 nas concentrações testadas apresentaram efeitos inflamatórios in vivo, citotóxicos e inflamatórios in vitro. Estes achados atestam que nas condições experimentais utilizadas os NCs estudados não são biocompatíveis. / Mestre em Odontologia