Orientador: Miguel Jafelicci Júnior / Banca: Antonio Tallarico Vicente Adorno / Banca: Humberto Osorio Stumpf / Banca: Adelino de Aguiar Coelho / Banca: Herbert Winnischofer / Resumo: A proposta deste estudo foi introduzir novos namomateriais para avaliar o efeito magnetocalórico (EMC). O EMC foi obtido a partir de medidas de uma família de isotermas de magnetização em um intervalo de temperatura e a mudança de entropia do sistema (ΔS) foi calculado usando as relações de Maxwell. Três tipos de materiais foram obtidos neste trabalho. O primeiro marterial foi as ferritas de gadolinío sintetizadas pelo processo poliol usando acetilacetonato de gadolínio e acetilacetonado de ferro como precursores metálicos e tetraetilenoglicol como solvente. O valor de mudança de entropia alcançou o valor máximo de 0,16 J Kg-1K-1 para campo de 2T, a baixa temperatura (30K). As propriedades magnéticas dos nanomateriais obtidos (Gd50FeOx, Gd5FeOx, Gd3FeOx e Gd1FeOx) foram obtidos em função da composição dos materiais. Moagem de alta energia foi empregada para produzir particulas pequenas de Gd5Si2Ge2. As propriedades magnéticas e magnetocalóricas das amostras bulk e moídas de Gd5Si2Ge2 foram investigadas a partir de medidas magnéticas. Quando comparado com o material bulk primitivo, diminuições significativas nos valores de magnetização de saturação e efeito magnetocalórico são observadas mesmo depois de pouco tempo de moagem, com 4h que produz partículas com distribuição de tamanho de 0,5μm. As amostras moídas parecem perder a transição estrutural de primeira ordem que aparece no Gd5Si2Ge2 bulk. Em baixas temperaturas as amostras moídas passam por uma transição de vidro de spin. Nanopartículas de FeAg foram sintetizadas através de modificações no processo poliol, usando acetilacetonato de prata e acetilacetonato de ferro como precursores e diferentes razões molares de Fe:Ag (1:1, 1:0,5 e 1:0,1, respectivamente). Os dados de difração de raios X mostram picos somente da prata na fase cúbico de face centrada. Os espectros de infravermelhos mostram... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The purpose of this study was to introduce new nanomaterial to evaluate magnetocaloric effect. The MCE was obtained by measuring a family of magnetization isotherms curves at set temperature intervals and calculating the entropy change (ΔS) for this system using the Maxwell relation. Three kinds of materials were made in this work. First material was gadolinium ferrites synthesized by polyol process using gadolinium acetilacetonate and iron acetilacetonate as metal precursors and tetraethileneglycol as solvent. The magnetic entropy change reaches the maximum values of 0.16 J Kg-1K-1 for the field of 2T, at low temperature (30K). The magnetic properties of the produced nanomaterials (Gd50FeOx, Gd5FeOx, Gd3FeOx and Gd1FeOx) were determined as a function of their composition. Highenergy ball milling was employed to produce small particles of Gd5Si2Ge2. Magnetic and magnetocaloric properties of the ball-milled and bulk Gd5Si2Ge2 samples were investigated through the magnetization measurements. When compared to the pristine bulk material, a significant decrease in saturation magnetization and magnetocaloric effect is observed even after the relatively short ball milling time of 4 h which produced particles with an average size of ca. 0.5 μm. The ball-milled samples appear to lose a first-order structural transition, present in bulk Gd5Si2Ge2, and display a superparamagnetic behaviour below the corresponding Curie temperatures. At very low temperatures, the Gd5Si2Ge2 ball-milled samples undergo a spin-glass transition. FeAg nanoparticles are synthesized by modified... (Complete abstract click electronic access below) / Doutor

abstract: Water-soluble, adenosine triphosphate (ATP)-stabilized palladium nanoparticles have been synthesized by reduction of palladium salt in the presence of excess ATP. They have been characterized by electron microscopy, energy dispersive X-ray spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy, and X-ray diffraction in order to determine particle size, shape, composition and crystal structure. The particles were then subsequently attached to a glassy carbon electrode (GCE) in order to explore their electrochemical properties with regard to hydrogen insertion in 1 M sodium hydroxide. The particles were found to be in the size range 2.5 to 4 nm with good size dispersion. The ATP capping ligand allowed the particles to be air-stable and re-dissolved without agglomeration. It was found that the NPs could be firmly attached to the working electrode via cycling the voltage repeatedly in a NP/phosphate solution. Further electrochemical experiments were conducted to investigate the adsorption and absorption of hydrogen in the NPs in 1 M sodium hydroxide. Results for cyclic voltammetry experiments were consistent with those for nanostructured and thin-film palladium in basic solution. Absorbed hydrogen content was analyzed as a function of potential. The maximum hydrogen:Pd ratio was found to be ~0.7, close the theoretical maximum value for β phase palladium hydride. / Dissertation/Thesis / M.S. Chemistry 2013

The synthesis, characterization and amphiphilic self-assembly of polymer brush functionalized nanoparticles (PBNPs) using a block copolymer template is described herein. To study the effect of polymer brush composition on self-assembly, four samples were created using a mixture of PS-b-PAA (polystyrene-block-polyacrylic acid) and PMMA-b-PAA (poly(methyl methacrylate)-block-polyacrylic acid) diblock copolymers to create PBNPs with a CdS quantum dot (QD) core and different ratios of PS and PMMA in the coronal brush. Static light scattering showed that despite differences in brush composition, the PBNPs formed nanoparticles of similar aggregation number and chain density but showed evidence of asymmetric structure in a common solvent for both blocks at higher PS contents. After subsequent hydrolysis of the hydrophobic PMMA to hydrophilic poly(methacrylic acid) (PMAA), these amphiphilic particles were then self-assembled in THF/H2O solution in which it was determined that increasing the hydrophobic content of the brush composition, the initial nanoparticle concentration (c0) or the added salt content (RNaCl), would cause the assembly of low curvature assemblies. Compilation of this data allowed for the construction of phase diagrams for PBNP systems based on brush composition and c0 at different salt contents. Lastly, PS-b-PAA-b-PMMA triblock copolymers with variable PMMA chain length were assembled into PBNPs around a CdS QD core using a block copolymer template approach. Light scattering showed these particles also had similar aggregation number and chain density despite the difference in PMMA chain length. After hydrolysis of PMMA to PMAA these particles were then self-assembled in THF/H2O mixtures to determine the role of PMAA block length on the produced morphological structures. The resulting assemblies suggest that chain length played a minimal role in their self-assembly / Graduate / 2018-09-15

This thesis includes three stages of experiments. The goal of the thesis was to prepare nanoparticle-encapsulated curcumin for the purpose of drug delivery. The first step was the nanoparticle preparation. The self-assembly of block copolymer (poly(ε- caprolactone)-b-poly(ethylene oxide)) and curcumin was conducted on a gas-liquid two phase microfluidic reactor. During preparation, various chemical parameters and flow rates were tested. The nanoparticles showed flow variability; the size decreased and the loading efficiency increased with increased flow rates. Increasing the water content and drug-to-polymer loading ratio also proved to increase loading efficiency and decrease the size of the nanoparticles. The release profiles, however, showed fast release rates under various preparation conditions, with a nearly complete release after ~5 h. In the next stage of the research, we considered release optimization in preparation for future pharmacokinetic studies. Increasing the flow rate had a greater influence on slowing down release rates than changing other parameters, such as decreasing the drug-to- polymer loading ratio or increasing the water content. A procedure to extract and quantify curcumin from mouse blood was also developed in this stage. In the final stage of the research, nanoparticle-encapsulated curcumin was tested on a human breast cancer cell line, MDA-MB-231. The result showed that the nanoparticle formulation had a growth inhibition effect on MDA-MB-231, although the cytotoxicity was compromised by encapsulation in the nanoparticles. / Graduate / 2019-01-13

Utilisation de nanoparticules pour délivrer des protéines dans les épithéliums respiratoires. Caractérisation des mécanismes impliqués. L’administration de médicaments par les voies respiratoires humaines est un domaine de la recherche en pleine expansion. Un effort croissant est porté sur le développement de systèmes innovants capables d’échapper aux mécanismes de clairance des voies respiratoires, d’améliorer la biodisponibilité des molécules d’intérêt, leur absorption dans la muqueuse et leur efficacité thérapeutique. Dans ce contexte, le but de ce travail était d’évaluer le potentiel de nanoparticules polysaccharidiques cationiques et poreuses (NP+) comme vecteurs de protéines à travers les voies respiratoires humaines. Les NP+ sont utilisées avec succès in vivo, comme vecteurs mucosaux dans de nombreuses applications telles que la vaccination, l’allergie, la thérapie anticancéreuse et la délivrance de molécules thérapeutiques. Cependant, les mécanismes d’interaction de ces nanoparticules avec les cellules épithéliales des voies respiratoires sont peu connus. Nous avons étudié l’endocytose, l’exocytose et la localisation intracellulaire de ces nanoparticules dans des cellules épithéliales bronchiques humaines. Leur toxicité a été évaluée sur ces cellules et plus particulièrement leur cytotoxicité et leur génotoxicité. Enfin, nous avons étudié et caractérisé les mécanismes de délivrance intracellulaire de protéines par ces nanoparticules et l’influence de leur composition interne sur ces mécanismes. Nos travaux montrent une endocytose rapide des NP+ par la voie des clathrines, ainsi qu’une importante exocytose par des mécanismes dépendant du cholestérol. Elles sont localisées dans les vésicules de clathrines, les endosomes précoces et pas dans les endosomes tardifs, ni dans les lysosomes. De manière ces nanoparticules s’associent quantitativement aux protéines et augmentent leur délivrance intracellulaire, tout en les protégeant de l’hydrolyse enzymatique à pH physiologique. De plus, la présence de lipides anioniques dans leur structure interne influence significativement les mécanismes d’interactions avec les cellules et de délivrance intracellulaire de protéines. Enfin, les études de toxicité ne montrent aucune cytotoxicité ni génotoxicité à des concentrations < 326 µg/cm2. Ces concentrations sont toutefois très élevées et difficilement atteignables in vivo. En conclusion, les NP+ ne sont pas toxiques sur les cellules épithéliales des voies respiratoires, elles interagissant fortement avec celles-ci et augmentent significativement la délivrance de protéines. Ce travail souligne l’intérêt de développer ce type de nanoparticules pour la délivrance de molécules d’intérêt pharmaceutique à travers les voies respiratoires humaines. / Drug delivery through the human respiratory tract is a promising field under investigation. A growing effort is focused on developing innovative delivery systems able to escape the clearance mechanisms of the respiratory tract, to improve molecules bioavailability, their absorption and their therapeutic efficacy, in the respiratory mucosa. In this context, the aim of this study was to evaluate the potential of polysaccharide cationic porous nanoparticles (NP+) as airway vectors for proteins. NP+ are successfully used as mucosal vectors in vivo, in many applications, including vaccination, allergy, cancer therapy and drug delivery. However, the mechanisms of NP+ interaction with airway epithelial cells remain poorly understood. We investigated the endocytosis, the exocytosis and the intracellular localization of NP+ in human bronchial epithelial cells. We assessed their toxicity on these cells, and particularly their cyto- and genotoxicity. Finally, we studied and characterized the mechanisms of intracellular delivery of proteins by these nanoparticles, and the influence of their inner composition, on these mechanisms. Our results showed a rapid uptake of NP+ via the clathrin endocytosis pathway, and a significant exocytosis via a cholesterol-dependent mechanism. Moreover, NP+ were located in clathrin vesicles, early endosomes but not in late endosomes nor lysosomes. Interestingly, these nanoparticles quantitatively associated proteins and increased their intracellular delivery, while protecting them from enzymatic degradation at physiological pH. Moreover, the presence of anionic lipids in their inner structure significantly influences their interaction with cells and the mechanisms of intracellular delivery. Finally, toxicity studies show no genotoxicity or cytotoxicity of these nanoparticles at concentrations below 326&#956;g/cm². However, these concentrations are very high and hardly realistic in vivo. In summary, NP+ are not toxic to airway epithelial cells, they strongly interact with these cells and significantly increase protein delivery. This work highlights the importance of developing this type of nanoparticles to deliver molecules via the human respiratory tract.

Ph.D. (Chemistry) / This study discusses the preparation of various sized dendrimer encapsulated ruthenium nanoparticles (RuDEN) with the use of the generation 4 (G4), generation 5 (G5) and generation 6 (G6) hydroxyl-terminated poly(amidoamine) (PAMAM-OH) dendrimers as templating agents. The size of the nanoparticles ranges from 1.1-2.2 nm. The RuDENs were used as nanoparticle solutions in catalytic reactions or immobilised on amorphous silica 60 and silica 100 and subsequently referred to as RuSil catalysts. These catalysts were evaluated in the reduction of 4-nitrophenol, toluene hydrogenation, citral hydrogenation, cinnamaldehyde hydrogenation and styrene oxidation...

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>Magister Scientiae - MSc / Magnetosomes, produced by magnetotactic bacteria (MTB), are the most attractive alternative source of non-toxic biocompatible magnetic nanoparticles (MNPs). A magnetosome contains Fe2O4 magnetite with properties superior to MNPs synthesized by the traditional chemical route. However, synthesis of magnetosomes on large scale has not been achieved yet because magnetotactic bacteria are fastidious to grow. In addition, magnetosomes are generally “soft” magnetic materials which can only be used for some applications, while other applications require “hard” magnetic materials. Here at the Institute of Microbial Biotechnology and Metagenomic (IMBM), a study is being conducted on cloning and expression of the magnetosome gene island (MIA), the genetic machinery for magnetosome formation, in an easy to culture E. coli strain. The magnetic properties of the magnetosome can be manipulated by doping with divalent metals such as Ni2+ or Co2+ for a variety of applications. The specific objective of this study was to genetically engineer E. coli strains which accumulate intracellular Ni2+ or Co2+ in order to manipulate the magnetic properties of the magnetosomes. Three E. coli mutants and a wild type strain were transformed with high affinity Ni2+ or Co2+ uptake genes and evaluated for intracellular accumulation at different medium concentrations of NiCl2 or CoCl2. Cellular iron and magnesium were also evaluated because iron is the major component of the magnetosome and magnesium is important for cell growth. The wild type strain, EPI 300 habouring Ni2+ uptake permease the hoxN gene or Co2+ uptake ABC type transporter cbiKMQO operon was found to accumulate the most intracellular Ni2+ or Co2+ in medium conditions most likely to induce magnetosome formation and magnetite manipulation. This strain can be used to co-express the MIA and Ni2+ or Co2+ uptake gene for mass production of magnetosome with altered magnetic properties.

Efforts to discover an efficient yet environmentally friendly mode of metal nanoparticle (NP) synthesis are increasing rapidly. A ‘green’ route that avoids the high costs, toxic wastes and complicated protocols associated with chemical synthesis methods is therefore highly sought after. A biologically based protocol will provide the possibility of gaining control over the mechanism merely by manipulating the experimental conditions of the system. Given that the properties of nanoparticles are highly dependant on the morphology of the particles themselves, this mechanistic control will provide significant industrial advantages with regards to tailoring specific properties of the nanoparticles produced. The key objectives of this study were to: a) determine whether a consortium of sulfate-reducing bacteria was capable of platinum nanoparticle synthesis, b) elucidate the bioreductive, enzymatic mechanism responsible, and c) attempt to control the morphologies of the particles produced. A consortium of sulfate-reducing bacteria (SRB), isolated from sewage sludge, was used in these investigations due to the advantages a consortium provides in comparison to pure cultures. The syntrophic relationships established within the constituent species not only prevent the growth of contaminant microbes, but increases the oxygen-tolerance of the system as a whole. The sulfate-reducing consortium was shown to possess an aerobic mechanism for Pt(IV) reduction which, though different from the anaerobic bioreductive mechanism previously identified in literature, did not require an exogenous electron donor. It was demonstrated that the Pt(IV) ion becomes reduced to Pt(0) via a two-cycle mechanism involving Pt(II) as the intermediate. Further investigation elucidated the reduction of Pt(IV) to Pt(II) to be dependant on a novel Pt(IV) reductase which becomes upregulated in the presence of Cu(II), while the reduction of Pt(II) to Pt(0) occurred by means of a periplasmic hydrogenase. To our knowledge, this is the first time a coupled mechanism for Pt(IV) reduction by micro-organisms has been proposed. A cell-free, crude protein solution from the consortium produced both geometric and irregular platinum nanoparticles. The wavelength of 334 nm was chosen as a nonquantitative indicator of Pt(0) nanoparticle formation over time. The optimum conditions for nanoparticle synthesis were pH 9.0, 65 ˚C and 0.75 mM Pt(IV) as H2PtCl6 salt. In the absence of a buffer a Pt(IV) concentration > 1 mM resulted in the precipitation of protein-nanoparticle bioconjugates, due to unfavourable acidic conditions. This demonstrated that the nanoparticles were binding to and becoming stabilised by general protein in the cell-free solution. Upon addition of a sodium-bicarbonate buffer, a general increase in Pt(IV) reduction to Pt(II) was observed. The addition of the buffer also resulted in an unexplained change in particle morphology and for this reason was not used in subsequent investigations. Polyvinylpyrrolidone (PVP) was shown to compromise the reduction rate of the Pt(IV) ion by SRB cells. The presence of extracellular NP’s was suggested by the colour of the supernatant turning brown and the A334 increasing over time. Attempts to visualise the particles by transmission electron microscopy (TEM) resulted in an unexpected phenomenon where nanoparticles could be observed to form dynamically upon irradiation by the electron beam. Extended irradiation by the electron beam also resulted in structural changes of the particles occurring during observation. An increase in temperature was shown to increase the reduction rate which in turn resulted in particles decreasing in size. The starting pH was shown to have a significant effect on the reduction rate and particle morphology although specific trends could not be identified. In conclusion, the cell-soluble extract from the sulfate-reducing consortium investigated, is capable of Pt(0) nanoparticle synthesis. Precise control over the particle morphology was not attained although the mechanism was further clarified and optimal conditions for nanoparticle synthesis were determined.

Ferrihydrite (FHYD), a nanocrystalline material has long been described as a poorly crystalline disordered mineral mainly due to its small crystal size which is typically 2−6 𝑛𝑚. The three-dimensional structure of the mineral has long been described by a multi-phase structural model that consists of Fe3+ only in octahedral (Oh) coordination. In this model ferrihydrite is described as a mixture of two major phases (akaganeite/goethite-like f-phase and feroxyhite-like d-phase) and a minor ultradispersed nanohematite phase. This model has been recently challenged and a new, single-phase model was proposed, having a basic structural motif closely related to the Baker-Figgs δ-Keggin cluster and is isostructural with the mineral akdalaite, Al10O14(OH)2. In its ideal form, the proposed new structure of FHYD consist of 80 % Oh and 20 % tetrahedral (Td) Fe3+ polyhedra which can be adequately described by a single-domain model with the hexagonal spacegroup 𝑃63𝑚𝑐 and unit cell dimensions 𝑎=5.95 Å and 𝑐=9.06 Å. In this study, nanoparticles of 2-line FHYD (FHYD2), 2-line FHYD deposited onto SiO2 (FHYD2/SiO2) and 6-line FHYD (FHYD6) synthesised using rapid hydrolysis of Fe(NO3)3.9H2O solutions were characterized using X-ray diffraction (XRD), Raman spectroscopy, transmission electron microscopy (TEM), Mössbauer spectroscopy (MS) as well as magnetization and magnetic susceptibility measurements. The coordination environment of iron atoms in the structure of FHYD was investigated using TEM and MS. The thermal transformation of FHYD nanoparticles was monitored through changes in the magnetization as a function of temperature and the reduction behaviour in hydrogen environment was studied using temperature programmed reduction (TPR), in-situ XRD and MS. Electron diffraction, TEM/ scanning TEM (STEM) imaging, and electron energy loss (EELS) measurements were carried out on three different microscopes viz. JEOL JEM-2100 LaB6 TEM, aberration corrected Schottky-FEG JEOL JEM-ARM200F HRTEM and cold-FEG Zeiss SESAM TEM. EELS studies were concentrated mainly on the iron 𝐿-edge of FHYD and iron oxides reference spectra with well known crystal structures. The iron oxide Fe 𝐿-edge is usually characterized by two intense sharp peaks termed “white lines”. The fine structures introduced by the crystal field effect on the 𝐿- edge contain information that is highly specific to the Fe3+ site symmetry.