Stem cell therapies hold great promise for diseases such as stroke, where few effective treatment options exist. Clinical translation of experimental stem cell therapies requires the ability to monitor delivery and behaviour of cells non-invasively in-vivo with clinical imaging modalities such as MRI. This thesis presents the translation of established methods for labelling and imaging stem cells with specialized MRI systems to a more clinically relevant setting. A methodology for harvesting and labelling a cell population containing stem cells with iron oxide for detection with a clinical MRI system is presented and single cell detection is demonstrated in-vitro. The feasibility of detecting iron oxide labelled stem cells intravenously delivered in a rat model of stroke is tested. Results demonstrate that while MRI is highly sensitive to the presence and distribution of iron oxide containing cells in-vivo the true origin of these cells remains ambiguous with the current methodology.

Stem cell therapies hold great promise for diseases such as stroke, where few effective treatment options exist. Clinical translation of experimental stem cell therapies requires the ability to monitor delivery and behaviour of cells non-invasively in-vivo with clinical imaging modalities such as MRI. This thesis presents the translation of established methods for labelling and imaging stem cells with specialized MRI systems to a more clinically relevant setting. A methodology for harvesting and labelling a cell population containing stem cells with iron oxide for detection with a clinical MRI system is presented and single cell detection is demonstrated in-vitro. The feasibility of detecting iron oxide labelled stem cells intravenously delivered in a rat model of stroke is tested. Results demonstrate that while MRI is highly sensitive to the presence and distribution of iron oxide containing cells in-vivo the true origin of these cells remains ambiguous with the current methodology.

>Magister Scientiae - MSc / Magnetic luminescent nanoparticles of an iron oxide (Fe₃O₄) superparamagnetic core and an indium phosphide/zinc selenide (InP/ZnSe) quantum dot shell are reported. The magnetic nanoparticles (MNP’s) and quantum dots (QD’s) were each synthesized separately before conjugation. The MNP’s were functionalized with a thiol-group allowing the QD shell to bind to the surface of the MNP by the formation of a thiol-metal bond. The nanocomposite was capped with 3-mercaptopropionic acid, 1-propanethiol, 2-methyl-1-propanethiol and their properties investigated using the characterization techniques: high- resolution transmission electron microscopy (HR-TEM), energy-dispersive spectroscopy (EDS), UV-vis, scanning electron microscopy (SEM), superconducting quantum interference device (SQUID), and photoluminescence. These techniques yielded significant information on particle size, morphology, dispersion, and chemical composition including luminescence and florescence.

Stable suspensions of superparamagnetic cobalt nanoparticles have been prepared in poly(dimethysiloxane) (PDMS) carrier fluids in the presence of poly[dimethylsiloxane-b-(3-cyanopropyl)methylsiloxane-b-dimethylsiloxane] (PDMS-PCPMS-PDMS) triblock copolymers as steric stabilizers. A series of the polysiloxane triblock copolymers with systematically varied molecular weights were prepared via anionic polymerization using LiOH as an initiator. These copolymers formed micelles in toluene or poly(dimethylsiloxane) (PDMS) carrier fluids and served as "nanoreactors" for thermal decomposition of the CO₂(CO)8 precursor. The nitrile groups on the PCPMS central blocks are thought to coordinate onto the particle surface, while the PDMS endblocks protrude into the reaction medium to provide steric stability. The particle size can be controlled by adjusting the cobalt to copolymer ratio. Ordered self-assemblies of these cobalt nanoparticles are observed when the dispersions are cast from toluene. Electron diffraction spectroscopy reveals that the cobalt nanoparticles have fcc crystal structures. TEM shows non-aggregated cobalt nanoparticles with narrow size distributions, which are evenly surrounded with copolymer sheaths. However, some degree of surface oxidation was observed over time, resulting in a decrease in magnetic susceptibility. Novel poly[dimethylsiloxane-b-methyltriethoxysilylsiloxane-b-(3-cyanopropyl) methylsiloxane-b-methyltriethoxysilylsiloxane-b-dimethylsiloxane] (PDMS-PMTEOS-PCPMS-PMTEOS-PDMS) pentablock terpolymers were prepared. These terpolymers could fill the dual role both as steric stabilizers for preparing stable cobalt nanoparticle dispersions and precursors for the particle coating process. Silica films coated on the particles surfaces were employed to prevent the surface oxidation of the nanoparticles. Specific saturation magnetic measurement indicates that coating the nanoparticles with silica thin films can effectively inhibit the oxidation process. / Ph. D.

Atualmente, as nanopartículas superparamagnéticas despertam enorme interesse científico devido sua grande variedade de aplicações em biomedicina, tanto na área de diagnóstico quanto no tratamento de enfermidades. Embora muitos materiais vem sendo estudados, os óxidos de ferro (magnetita e maghemita) apresentam maiores avanços nos estudos para aplicações em medicina. A preferência por óxidos de ferro se deve a baixa toxicidade destas partículas quando comparado as nanopartículas metálicas ou ligas. Entretanto, as nanopartículas destes óxidos possuem baixas magnetizações de saturação que diminuem ainda mais com as sucessivas etapas de recobrimento necessárias para conferir funcionalidade a estas partículas. Desse modo, há uma necessidade atual para o desenvolvimento de nanopartículas superparamagnéticas com elevada magnetização, baixa toxicidade e maior facilidade de funcionalização da sua superfície com biopolímeros e agentes funcionalizantes. Neste trabalho, nanopartículas superparamagnéticas de cobalto metálico e ferrita de cobalto foram sintetizadas e suas propriedades magnéticas foram comparadas com a magnetita. Nanopartículas de cobalto foram escolhidas, pois seu elevado comportamento ferromagnético é menor apenas que o ferro metálico, além do baixo custo de seus reagentes. As nanopartículas magnéticas foram sintetizadas pelos métodos de microemulsão e decomposição térmica (baseado no método poliol) e suas composições química, estrutural, tamanho e distribuição de tamanho foram devidamente determinadas. Além disso, as nanopartículas de cobalto metálico e ferrita de cobalto foram recobertas com ouro utilizando o método de crescimento mediado por semente. Os sistemas microemulsionados utilizados neste trabalho não foram eficientes nem na síntese de nanopartículas estáveis de cobalto metálico nem no seu esperado controle morfológico. Já o método de decomposição térmica resultou em um rigoroso controle de composição química, estrutural e morfológico para as diferentes nanopartículas sintetizadas. O recobrimento com ouro foi efetivo na proteção do núcleo magnético e adicionalmente conferiu estabilidade, baixa toxicidade e bifuncionalidade às nanopartículas magnéticas através do seu fenômeno de ressonância plasmônica de superfície o qual foi preservado na nanoestrutura core@shell. O comportamento superparamagnético das nanopartículas de cobalto metálico recobertas com ouro e sua elevada magnetização de saturação foram expressivamente intensificadas quando comparadas as nanopartículas de magnetita sem recobrimento. Portanto, as nanopartículas sintetizadas neste trabalho apresentam propriedades de superfície e magnéticas otimizadas demonstrando um bom potencial para aplicações em biomedicina como sensores bifuncionais óptico-magnético. / Superparamagnetic nanoparticles have been extensively studied because its wide range of biomedical applications in both diagnostic and therapy areas. Although different materials are currently investigated, superparamagnetic iron oxides nanoparticles (SPION), magnetite and maghemite, are the most extensively studied for applications in medicine. The lower toxicity profile of the SPION becomes the most attractive than metal or alloys nanoparticles. Nevertheless, iron oxides nanoparticles have low saturation magnetization, which further decreases due to successive coats to provide their functionality, leading the actual demand to develop superparamagnetic nanoparticles with high magnetization, low toxicity and easy surface functionalization with biocompatible agents. In this work, superparamagnetic nanoparticles of metallic cobalt and cobalt ferrite were synthesized and their magnetic properties were compared with the magnetite SPION. Cobalt nanoparticles were chosen because present high ferromagnetic behavior among chemical elements, second only to iron, besides their low cost. The magnetic nanoparticles were synthesized by both microemulsion and thermal decomposition (based on the polyol process) methods and their chemical composition, structure, size and size distribution were properly characterized. In addition, the ferrite and metallic cobalt nanoparticles were coated with gold by using the seed-mediated growth method. The used microemulsion systems were not efficient enough to synthesize stable metallic nanoparticles and to promote the expected morphological control even to ferrites. Instead, the thermal decomposition processes resulted in rigorous control of chemical compositional, structure and morphology in all different prepared samples. Au-coating process was effective to protect the magnetic nuclei also giving additional stability, low toxicity and a bifunctionality to the magnetic nanoparticle since their surface plasmon resonance phenomenon was preserved in the core@shell nanostructure. The superparamagnetic behavior of the Au-coated cobalt nanoparticle was preserved and their saturation magnetization was significantly increased compared with the naked magnetite SPION. In conclusion, the synthesized nanoparticles present enhanced magnetic and surface properties showing good potential to be used in biomedical application as bifunctional optical-magnetic sensor.

Esta tese descreve o desenvolvimento de aplicações de nanopartículas superparamagnéticas de magnetita, devidamente funcionalizadas, nas seguintes áreas: Sensoriamento - As nanopartículas superparamagnéticas foram utilizadas em conjunto com um pequeno sistema analítico especialmente desenvolvido para esse trabalho, na análise de diversos metais pesados de grande relevância ambiental. O ponto de destaque da metodologia é o grande incremento em intensidade do sinal analítico em função da pré-concentração que pode ser realizada mediante utilização das nanopartículas superparamagnéticas e aplicação de um campo magnético externo. Remediação ambiental - A grande afinidade das nanopartículas por diversos materiais foi aproveitada na obtenção de um sistema de remediação ambiental que combina as propriedades magnéticas das nanopartículas e as propriedades adsorventes de carvão ativado. Esse sistema foi testado em contaminantes orgânicos e inorgânicos e permite uma maneira eficiente e inovadora de remoção de contaminantes em meio aquoso. Nanohidrometalurgia magnética - Os efeitos de pré-concentração de nanopartículas superparamagnéticas modificadas foram utilizados para melhorar a eficiência dos processos hidrometalúrgicos atuais para produção de cobre metálico a partir de minérios com baixa concentração do metal, chegando - se ao estado da arte da técnica. / This thesis describes the development of applications of superparamagnetic magnetite nanoparticles, properly functionalized, in the following areas: Sensing - The superparamagnetic nanoparticles were used in conjunction with a small analytical system specially developed in this work for analysis of several heavy metals of great environmental significance. The important point of this methodology is the general increase in intensity of the analytical signal as a function of pre-concentration may be performed by use of superparamagnetic nanoparticles under the influence of an external magnetic field. Environmental Remediation - The high affinity of nanoparticles for various materials was used to obtain an environmental remediation system that combines the properties of magnetic nanoparticles and the properties of activated carbon adsorbents. This system was tested in organic and inorganic contaminants and provides a novel and efficient removal of contaminants in the aqueous medium. Magnetic Nanohydrometalurgy - The effects of pre-concentration fro the funcionalized superparamagnetic nanoparticles modified were used to improve the efficiency of the actual hydrometallurgical processes used for production of metallic copper from ores with low concentration of metal, showing good perspectives of improving the state of the art of this technique.

Esta tese descreve o desenvolvimento de aplicações de nanopartículas superparamagnéticas de magnetita, devidamente funcionalizadas, nas seguintes áreas: Sensoriamento - As nanopartículas superparamagnéticas foram utilizadas em conjunto com um pequeno sistema analítico especialmente desenvolvido para esse trabalho, na análise de diversos metais pesados de grande relevância ambiental. O ponto de destaque da metodologia é o grande incremento em intensidade do sinal analítico em função da pré-concentração que pode ser realizada mediante utilização das nanopartículas superparamagnéticas e aplicação de um campo magnético externo. Remediação ambiental - A grande afinidade das nanopartículas por diversos materiais foi aproveitada na obtenção de um sistema de remediação ambiental que combina as propriedades magnéticas das nanopartículas e as propriedades adsorventes de carvão ativado. Esse sistema foi testado em contaminantes orgânicos e inorgânicos e permite uma maneira eficiente e inovadora de remoção de contaminantes em meio aquoso. Nanohidrometalurgia magnética - Os efeitos de pré-concentração de nanopartículas superparamagnéticas modificadas foram utilizados para melhorar a eficiência dos processos hidrometalúrgicos atuais para produção de cobre metálico a partir de minérios com baixa concentração do metal, chegando - se ao estado da arte da técnica. / This thesis describes the development of applications of superparamagnetic magnetite nanoparticles, properly functionalized, in the following areas: Sensing - The superparamagnetic nanoparticles were used in conjunction with a small analytical system specially developed in this work for analysis of several heavy metals of great environmental significance. The important point of this methodology is the general increase in intensity of the analytical signal as a function of pre-concentration may be performed by use of superparamagnetic nanoparticles under the influence of an external magnetic field. Environmental Remediation - The high affinity of nanoparticles for various materials was used to obtain an environmental remediation system that combines the properties of magnetic nanoparticles and the properties of activated carbon adsorbents. This system was tested in organic and inorganic contaminants and provides a novel and efficient removal of contaminants in the aqueous medium. Magnetic Nanohydrometalurgy - The effects of pre-concentration fro the funcionalized superparamagnetic nanoparticles modified were used to improve the efficiency of the actual hydrometallurgical processes used for production of metallic copper from ores with low concentration of metal, showing good perspectives of improving the state of the art of this technique.

Nano-sized particles are widely regarded as a tool to study biological events at cellular and molecular levels. However, there are only a few imaging modalities that can visualize interactions between nanoparticles and living cells. A new technique -- pulsed magneto-motive ultrasound imaging, capable of in-vivo imaging of magnetic nanoparticles at improved depth and in real-time is introduced in this study. In pulsed magneto-motive ultrasound imaging, an external high-strength pulsed magnetic field is applied to induce motion within magnetically labeled tissue and ultrasound is used to detect the induced internal tissue motion. A laboratory prototype of a pulsed magneto- motive ultrasound imaging system was built, tested and optimized through modeling and experimental studies using tissue-mimicking phantoms, ex-vivo tissue samples and in- vivo mouse tumor model. The results demonstrated a sufficient contrast between normal and iron-laden tissue labeled with ultra-small magnetic nanoparticles. Finally, further modifications and research directions are discussed which can eventually lead to development of a clinically applicable pulsed magneto-motive ultrasound imaging system. / text

Made available in DSpace on 2014-12-17T14:07:14Z (GMT). No. of bitstreams: 1 TharsiaCCC_TESE.pdf: 4165596 bytes, checksum: b73b464d52ff23430b153992ec45405a (MD5) Previous issue date: 2013-04-25 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / This work aims at obtaining nanoparticles of iron oxide, the magnetite one (Fe3O4), via synthesis by thermal decomposition through polyol. Thus, two routes were evaluated: a simple decomposition route assisted by reflux and a hydrothermal route both without synthetic air atmosphere using a synthesis temperature of 260?C. In this work observed the influence of the observe of surfactants which are generally applied in the synthesis of iron oxide nanoparticles decreasing cluster areas. Further, was observed pure magnetite phase without secondary phases generally found in the iron oxide synthesis, a better control of crystallite size, morphology, crystal structure and magnetic behavior. Finally, the introduction of hydroxyl groups on the nanoparticles surface was analyzed besides its employment in the polymer production with OH radicals. The obtained materials were characterized by XRD, DLS, VSM, TEM, TG and DSC analyses. The results for the magnetite obtainment with a particle size greater than 5 nm and smaller than 11 nm, well defined morphology and good magnetic properties with superparamagnetic behavior. The reflux synthesis was more efficient in the deposition of the hydroxyl groups on the nanoparticles surface / O objetivo desse trabalho foi a obten??o de nanopart?culas de ?xido de ferro, a magnetita (Fe3O4), via s?ntese por decomposi??o t?rmica via poliol, avaliando assim duas rotas: a rota simples decomposi??o assistida por refluxo e a rota hidrot?rmica, ambas sem atmosfera de ar sint?tico e usando a temperatura de s?ntese de 260?C. Observou-se nesse trabalho a influ?ncia da aus?ncia de surfactantes, comumente utilizados em s?nteses de ?xidos de ferro, com a finalidade de promover uma melhor dispers?o das nanopart?culas, diminuindo assim as ?reas de aglomerados. Al?m disso, visou-se: a obten??o de uma fase puramente de magnetita, sem a forma??o de fases secund?rias comumente encontradas nas s?nteses dos ?xidos de ferro; um melhor controle do tamanho de cristalito; da morfologia; da estrutura cristalina e do comportamento magn?tico. Por fim, analisou-se a introdu??o dos grupos hidroxilas na superf?cie das nanopart?culas, e sua empregabilidade na produ??o de pol?meros com radicais (OH). Os materiais obtidos foram caracterizados por an?lises de DRX, DLS, VSM, TEM, TG e DSC. Os resultados foram satisfat?rios quanto ? obten??o da magnetita, com tamanho de part?cula maior que 5 nm e menor que 11 nm, de morfologia bem definida e com boas propriedades magn?ticas com comportamento superparamagn?tico. Quanto ? deposi??o dos grupos de hidroxilas na superf?cie das nanopart?culas, a s?ntese com refluxo mostrou-se mais eficiente

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Porphyrins are very attractive system to study self-assembly due to its basic structure, chemical and thermal stability, synthetic versatility and important technological applications. This work presents the development of self-assembled systems meso-porphyrin derived from cardanol, the major constituent of the LCC. We were developed Langmuir and Langmuir-Blodgett (LB) thin films and superparamagnetic nanosystems coated with meso-porphyrin. The Langmuir films showed molecular area mean of the 177 à 2 confirmed by compressibility modulus. The 700 nm band observed in the Langmuir films supports the coexistence of monomers and dimers similar to the spectra of the solution (CHCl3/CH3COOH). The Brewster angle microscopy measurements showed formation of bright block domains with different sizes and shapes for the monolayer that disappears after surface pressure starts to increase. The UVâvis spectra of the Langmuir films and FTIR reflection of the LangmuirâBlodgett films (LB) indicated that the molecules exhibit preferential orientation with the parallel planes to the water (Langmuir) and in the substrate (LB). The LB film of 5 layers showed better response as electrode and has been tested as a promethazine sensor. Magnetic Fe 3 O 4 nanoparticles with an average size of 11 nm were coated with oleic acid layer and a meso-porphyrin layer to producing a novel superparamagnetic fluorescent nanosystem. Also were obtained systems coated with meso-porphyrins metallated with Co2+, Ni2+, Cu2+ and Zn2+ ions. The systems were characterized by TEM, FT-IR, TGA, vibrating sample magnetometry, UV-Vis, fluorescence and confocal miscroscopy. The systems showed good thermal stability, excellent magnetization and nanosized dimensions. / Porfirinas sÃo sistemas muito atrativos para estudos de automontagem graÃas a suaestrutura ba se, estabilidadequÃmica e tÃrmica, versatilidade sintÃtica e importantes aplicaÃÃes tecnolÃgicas. Este trabalho tem por finalidade apresentar o desenvolvimento de sistemas automontados da meso-porfirina derivada do cardanol, constituinte majoritÃrio do LCC. Foram desenvolvidos filmes finos de Langmuir e Langmuir-Blodgett (LB) e aplicado como sensor eletroquÃmico para prometazina e nanossistemas superparamagnÃticos revestidos com a meso-porfirina. Os filmes de Langmuir apresentaram Ãrea molecular mÃdia de 177 à 2 , confirmado pelo mÃdulo de compressibilidade. A banda centrada em λ = 700 nm observados nos filmes suporta a coexistÃncia de monÃmeros e dÃmeros semelhantes aos espectros em soluÃÃo de CHCl3/CH3COOH. A microscopia do Ãngulo de Brewster mostrou domÃnios com blocos brilhantes de diferentes tamanhos e formas para a monocamada que desapareceram apÃs o aumento da pressÃo de superfÃcie. Os espectros de UV-vis dos filmes e FT-IR no modo reflexÃo dos filmes de Langmuir-Blodgett (LB) indicaram que as molÃculas apresentam orientaÃÃo preferencial com os planos paralelos à Ãgua (no Langmuir) e no substrato (LB). O filme LB de 5 camadas apresentou melhor resposta como eletrodo e foi testado como um sensor de prometazina. As nanopartÃculas magnÃticas de Fe 3 O 4 com tamanho mÃdio de 11 nm foram revestidos com uma camada de Ãcido oleico seguido da meso-porfirina produzindo um novo nanossistema superparamagnÃtico fluorescente. Foram obtidos tambÃm os sistemas revestidos com porfirinas metaladas com os Ãons Co2+, Ni2+, Cu2+ e Zn2+, os quais foram caracterizados por MET, FT-IR, anÃlise termogravimÃtrica, magnetometria de amostra vibrante, UV-Vis, emissÃo de fluorescÃncia e miscroscopia confocal. Os resultados mostraram que os sistemas apresentaram boa estabilidade tÃrmica, comportamento superparamagnÃtico e dimensÃes nanomÃtricas.