Thesis--Lund Institute of Technology, 1994.

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CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / No presente trabalho, nanopartÃculas de M0,5Zn0,5Fe2O4 (M= Ni ou Mn) foram preparadas por sÃntese hidrotÃrmica sob condiÃÃes brandas sem qualquer procedimento de calcinaÃÃo. Amostras de composiÃÃo MFe2O4 (M = Zn, Ni ou Mn) tambÃm foram sintetizadas para fins de comparaÃÃo. As propriedades estruturais e magnÃticas das amostras foram investigadas por DifraÃÃo de Raios-X (DRX), Espectroscopia na RegiÃo do Infravermelho com Transformada de Fourier (FTIR), Espectroscopia Raman, Espectroscopia MÃssbauer, MagnetÃmetro de Amostra Vibrante (VSM) e Microscopia EletrÃnica de TransmissÃo (TEM). As anÃlises de DRX exibiram picos caracterÃsticos da fase de espinÃlio em todas as amostras sintetizadas. O tamanho mÃdio de partÃcula foi obtido por DRX, VSM e TEM e apresentou valor em torno de 10 nm para o M0,5Zn0,5Fe2O4. As imagens de TEM exibiram nanopartÃculas de morfologia cÃbica. Os parÃmetros magnÃticos observados por MÃssbauer e VSM mostraram comportamento superparamagnÃtico para todas as amostras contendo Zn, alÃm de altos valores de magnetizaÃÃo de saturaÃÃo (~55 meu/g) para a amostra Ni0,5Zn0,5Fe2O4. Devido a isto, este nÃcleo magnÃtico foi escolhido para a formulaÃÃo do nanocarreador. Desta forma, este foi inicialmente modificado com Ãcido olÃico. As anÃlises de TG e FTIR evidenciaram a presenÃa de molÃculas de oleato na superfÃcie da nanopartÃcula. AlÃm disso, o coeficiente de revestimento do processo realizado foi 3,7 oleato / nm2. Um estudo de adsorÃÃo da piplartina na nanopartÃcula modificada (NiZn-AO) foi realizado e observou-se relaÃÃo (NiZn-AO : Piplartina) Ãtima de 1 : 2 (m/m). ApÃs o processo adsortivo, o sistema contendo NiZn-AO e piplartina foi revestido com matriz polimÃrica constituÃda de P123 e F127 para conferir biocompatibilidade ao sistema, e formar o nanocarreador. Testes preliminares de hipertermia foram realizados na nanopartÃcula e observou-se que um campo de 126 Oe conduz a geraÃÃo de calor para alcanÃar uma temperatura de 42ÂC, dentro da faixa de hipertermia moderada. Portanto, o nanocarreador formulado apresenta potencial para aplicaÃÃes biomÃdicas. / In this work, nanoparticles of the M0,5Zn0,5Fe2O4 (M = Ni ou Mn) have been prepared by hydrothermal synthesis in mild conditions without any calcinations process. MFe2O4 (M = Zn, Ni or Mn) nanoparticles were also prepared for comparison. The structural and magnetic properties of the ferrites were investigated by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, MÃssbauer spectroscopy, vibrating sample magnetometer (VSM) and Transmission electron microscopy (TEM). XRD analysis showed peaks of the spinel phase for all samples. The average particle size was obtained by XRD, TEM and VSM and values around 10 nm were found for M0,5Zn0,5Fe2O4. TEM images showed particles of cubic morphology. The magnetic parameters observed by MÃssbauer and VSM shown superparamagnetic behavior for the samples containing Zn and high saturation magnetization values (~55 emu/g) for Ni0,5Zn0,5Fe2O4. Due to this, it was chosen for formulating the nanocarrier. Thus, it was first modified with oleic acid. The TG and FTIR analysis revealed the presence of oleate molecules on the surface of the nanoparticle. Furthermore, the coating coefficient of the process carried was 3.7 oleate / nm2. A study of piplartine adsorption on the modified nanoparticle (NiZn-AO) was performed and the optimum relationship (NiZn-AO: piplartine) was 1 : 2 (w / w). After the adsorptive process, the system containing NiZn-AO and piplartine was coated with polymeric matrix consisting of F127 and P123 to confer biocompatibility to the system and form the nanocarrier. Hyperthermia tests were performed in nanoparticles and it was observed that a field of 126 Oe leads to heat generation to attain a temperature of 42ÂC within the range of moderate hyperthermia. Therefore, the fabricated nanocarrier had potential for biomedical applications.

Submitted by Cássia Santos (cassia.bcufg@gmail.com) on 2016-09-26T11:37:12Z No. of bitstreams: 2 Tese - Marcus Carrião dos Santos - 2016.pdf: 18819776 bytes, checksum: c30d69dcb666acd99ab25efc73f7a96e (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-09-26T12:06:45Z (GMT) No. of bitstreams: 2 Tese - Marcus Carrião dos Santos - 2016.pdf: 18819776 bytes, checksum: c30d69dcb666acd99ab25efc73f7a96e (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2016-09-26T12:06:45Z (GMT). No. of bitstreams: 2 Tese - Marcus Carrião dos Santos - 2016.pdf: 18819776 bytes, checksum: c30d69dcb666acd99ab25efc73f7a96e (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-05-04 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / The phenomenon of heat dissipation by magnetic materials interacting with an alternating magnetic field, known as magnetic hyperthermia, is an emergent and promising therapy for many diseases, mainly cancer. The scientific community has endeavored to identify the properties that lead to maximum efficiency dissipation of magnetic nanoparticles. However, the diameter in which this efficiency reaches maximum is sometimes bigger than 10 nm, presenting several incompatibilities with biomedical aplications. On the other hand, small nanoparticles (< 8 nm}) do not suffer from the same disadvantages. On the contrary, they benefit from a biodistribution convenient for cancer treatment, affinity for the lymphatic system, further penetration of tumor tissue and renal clearance. However, the use of small nanostructures as heat centers never received much attention, in part because the model most used to describe the magnetic hyperthermia phenomenon, the linear response theory (LRT), provides a very small dissipation in these systems. Recently, experimental results have questioned this inefficiency and evidences that it is possible to produce a biological response (including cell death) without necessarily measuring a temperature variation opened up new possibilities for small nanostructures. This research, therefore, proposes a change in magnetic nanostructure tailoring strategy for biomedical applications of hyperthermia: to make more efficient dissipation in small nanoparticles. Therefore, it is necessary to rebuild the theoretical framework of hyperthermia, making the description of these small systems more accurate. This thesis deals with the development of modeling tools to enable a distinction between the most superficial and internal region of the nanoparticle, recognizing that many of the properties at the nanoscale has its origin in surface effects and the surface-to-volume ratio. A model for the description of core-shell system magnetization was developed, based on the Heisenberg Hamiltonian and a mean field theory in which different parameters may be assigned to each region. The combination of this model with the LRT has given rise to a new description of hyperthermia phenomenon in which the importance of surface effects and can be explicitly considered, making also possible the description of heterogeneous systems. The model was compared with original (homogeneous nanoparticles) and literature (heterogeneous nanoparticles) experimental data, with good qualitative agreement with the results. In an attempt to verify the influence of effects of nonlinearity in these systems, a non-linear response theory was developed from the generalization of the LRT, and applied to core-shell systems. The fundamental role of these theoretical tools is to point the direction in which the nanomaterials tailoring should advance to make viable the proposed hyperthermia with small nanostructures. The models proposed here suggest that a higher dissipation efficiency in small systems is obtained with a combination of materials which lead to the reduction ratio of shell-to-core damping factors, increasing of the exchange constant in the interface and maximizing the shell-to-core anisotropy constants, indicating that better results should be found in Soft@Hard systems. / O fenômeno de dissipação de calor por materiais magnéticos que interagem com um campo magnético alternado, conhecido como hipertermia magnética, é uma emergente e promissora terapia para muitas doenças, principalmente o câncer. A comunidade científica tem se esforçado para identificar as propriedades que levam à eficiência máxima de dissipação em nanopartículas magnéticas. Entretanto, muitas vezes, o diâmetro para o qual essa eficiência é máxima supera 10 nm, apresentando diversas incompatibilidades com as aplicações biomédicas. Por outro lado, nanopartículas pequenas (< 8 nm) não sofrem das mesmas desvantagens, pelo contrário, se beneficiam de uma biodistribuição conveniente para o tratamento oncológico, afinidade com o sistema linfático, maior penetração no tecido tumoral e excreção via depuração renal. Entretanto, o uso de nanoestruturas pequenas como centros de calor nunca recebeu muita atenção, em parte, porque o modelo mais utilizado para descrever o fenômeno de hipertermia magnética, a teoria de resposta linear (LRT), prevê uma dissipação muito pequena nesses sistemas. Recentemente, resultados experimentais colocaram em dúvida essa ineficiência e evidências de que é possível produzir uma resposta biológica (inclusive morte celular) sem necessariamente elevar a temperatura de forma mensurável abriram novas possibilidades para as nanoestruturas pequenas. Esse trabalho propõe, então, uma mudança na estratégia de engenharia de nanoestruturas magnéticas para aplicações biomédicas de hipertermia: que se busque tornar mais eficiente a dissipação em nanopartículas pequenas. Para tanto, é necessário reconstruir o arcabouço teórico de hipertermia, para tornar a descrição desses sistemas pequenos mais precisa. Esta tese ocupa-se do desenvolvimento de ferramentas de modelagem que permitam uma diferenciação entre a região mais superficial e interna da nanopartícula, reconhecendo que grande parte das propriedades em escala nanométrica tem sua origem nos efeitos de superfície e na relação superfície-volume. Um modelo de descrição da magnetização de sistemas core-shell foi desenvolvido, com base na hamiltoniana de Heisenberg e em uma teoria de campo médio, no qual podem ser atribuídos diferentes parâmetros para cada uma dessas regiões. A combinação desse modelo com a LRT deu origem a uma nova descrição do fenômeno de hipertermia no qual a importância de efeitos de superfície podem ser explicitamente considerados, tornando possível também a descrição de sistemas heterogêneos. O modelo foi comparado com dados experimentais originais (nanopartículas homogêneas) e da literatura (nanopartículas heterogêneas), apresentando boa concordância qualitativa com os resultados. Na tentativa de verificar a influência de efeitos de não-linearidade nesses sistemas, desenvolveu-se uma teoria de resposta não-linear a partir da generalização da LRT, aplicando-a a sistemas core-shell. O papel fundamental dessas ferramentas teóricas é apontar a direção para qual a engenharia de nanomateriais deve avançar para tornar a proposta de hipertermia com nanoestruturas pequenas viável. Os modelos propostos aqui sugerem que a maior eficiência de dissipação em sistemas pequenos será obtida com a combinação de materiais que levem à redução da razão entre os fatores de damping da shell com relação ao core, o aumento da constante de exchange na interface e a maximização da razão entre as constantes de anisotropia da shell com relação ao core, indicando melhores resultados para sistemas Soft@Hard.

In this dissertation, I present the results of a systematic study on novel multifunctional nanostructure systems for magnetic hyperthermia applications. All the samples have been synthesized, structurally/magnetically characterized, and tested for magnetic hyperthermia treatment at the Functional Materials Laboratory of the University South Florida. This work includes studies on four different systems: (i) Core/shell Fe/γ-Fe2O3 nanoparticles; (ii) Spherical and cubic exchange coupled FeO/Fe3O4 nanoparticles; (iii) Fe3O4 nano-octopods with different sizes; (iv) High aspect ratio FeCo nanowires and Fe3O4 nanorods. In particular, we demonstrated the enhancement of the heating efficiency of these nanostructures by creating monodisperse and highly crystalline nanoparticles, and tuning their magnetic properties, mainly their saturation magnetization (MS) and effective anisotropy, in controlled ways. In addition, we studied the influence of other parameters, such as the size and concentration of the nanoparticles, the magnitude of the applied AC magnetic field, or different media (agar vs. water), on the final heating efficiency of these nanoparticles. For the core/shell Fe/γ-Fe2O3 nanoparticles, a modest heating efficiency has been obtained, resulting mainly from the strong reduction in MS caused by the shrinkage of the core with time. However, for sizes above 14 nm, the shrinkage process is much slower and the obtained heating efficiency is better than the one exhibited by conventional solid nanoparticles of the same size. In the case of the exchange-coupled FeO/Fe3O4 nanoparticles, we successfully created two sets of comparable particles: spheres with 1.5 times larger MS than the cubes, and cubes with 1.5 times larger effective anisotropy than the spheres, while keeping the other parameters the same. Our results show that increasing the effective anisotropy of the nanoparticles gives rise to a greater heating efficiency than increasing their MS. The Fe3O4 nano-octopods, with enhanced surface anisotropy, present better heating efficiency than their spherical and cubic nanoparticles, especially in the high field region, and we have shown that by tuning their size and the effective anisotropy, we can optimize their heating response to the applied AC magnetic field. For magnetic fields, smaller than 300−400 Oe we found that the smallest nano-octopods give the best heating efficiency. Yet if we increase the AC field value, the bigger octopods show an increased heating efficiency and become more effective. Finally, the FeCo nanowires and Fe3O4 nanorods exhibit enhanced heating efficiency with increasing aspect ratio when aligned in the direction of the applied AC magnetic field, due to the combined effect of shape anisotropy and dipolar interactions. Of all the studied systems, these 1D high aspect ratio nanostructures have displayed the highest heating rates. All of these findings point toward an important fact that tuning the structural and magnetic parameters in general, and the effective anisotropy in particular, of the nanoparticles is a very promising approach for improving the heating efficiency of magnetic nanostructures for enhanced hyperthermia.

Near-infrared dyes can be used as theranostic agents in cancer management based on their optical imaging and localized hyperthermia capabilities. However, their clinical translatability is limited by issues such as photobleaching, short circulation times, and non-specific biodistribution. We studied the applications of IR820 in optical imaging and hyperthermia, and we prepared nanoconjugate formulations to overcome some of the aforementioned limitations. Free IR820 can be used for optical imaging, with a strong signal still present 24 hours after i.v. injection, an elimination plasma half-life in the order of hours, and primary biodistribution to liver, lung, and kidneys. After 808-mn laser exposure, IR820 can also raise in vitro temperatures to the 41-43°C range that can selectively inhibit cancer cell growth. We conjugated IR820 with PEG-diamine via ionic interactions to create nanoconjugates (IR820-PDNCs) with diameters of approximately 50-nm per SEM and a zeta potential of 2.0±0.9 mV. IR820-PDNCs enhanced cellular internalization compared to IR820 for imaging in SKOV-3, MES-SA, and Dx5 cancer cells. The nanoconjugates also significantly enhanced hyperthermia-mediated cytotoxicity in MES-SA and Dx5 compared to the free dye (p

Heat exposure causes several physiological and metabolic alterations. Although lipids are vital in sustaining energy production, heat-induced alterations in lipid metabolism have not been clearly established. CHAPTER 1 reviews the known metabolic alterations resulting from heat stress, with a specific focus on changes in whole-body lipid utilization and plasma lipids. CHAPTER 1also outlines the physiological changes caused by heat stress, and their role in reducing exercise performance. The study presented in CHAPTER 2 has shown that, compared to thermoneutral conditions, NEFA concentrations were 37% higher following passive heating and 34% higher following exercise in the heat, without significant changes in whole-body lipid utilization. In addition, the level of hyperthermia attained during passive pre-heating and exercise in the heat resulted in a 13% decrease in total external work and a significantly higher rate of perceived exertion. CHAPTER 3 summarizes the study results and presents the limitations and applications of the study.

The structural, electronic, magnetic, magnetocaloric, and transport properties of doped Ni-Mn-(In, Sn) based Heusler alloys were studied using neutron diffraction, x-ray diffraction (XRD), differential scanning calorimetry (DSC), high field magnetization, specific heat, x-ray absorption spectroscopy (XAS), x-ray magnetic circular dichroism (XMCD), and hydrostatic pressure measurements. The adiabatic temperature change (∆Tad) by a direct method and through thermomagnetic measurements in magnetic fields up to 14 T has been performed for these alloys. Also the mixed effect of pressure and magnetic field on the transition temperature of these alloys are discussed. In order to develop new magnetocaloric and multifunctional materials, the synthesis and characterization of Heusler alloys in reduced dimensions, i.e., ribbons and thin films has been performed. In addition, the structural, magnetic, and magnetocaloric properties of Ni-based binary alloys were investigated, including saturation magnetization and Curie temperature (TC) for the possible applications in self controlled magnetic hyperthermia applications.

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