Doutorado em Física (IF)
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Navegando Doutorado em Física (IF) por Por Orientador "Bakuzis, Andris Figueiroa"
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Item Efeito da interação dipolar magnética na eficiência de aquecimento de nanopartículas: Implicações para magnetohipertermia(Universidade Federal de Goiás, 2014-12-09) Branquinho, Luis Cesar; Bakuzis, Andris Figueiroa; http://lattes.cnpq.br/3477269475651042; Bakuzis, Andris Figueiroa; Pelegrini, Fernando; Franco Junior, Adolfo; Morais, Paulo Cesar de; Landi, Gabriel TeixeiraMagnetic nanoparticles can generate heat when submitted to alternating magnetic fields of adequate amplitude and frequency. This phenomenon is named magnetic hyperthermia and has several therapeutic applications, as for example, in the treatment of cancer. In general, the theoretical models used to describe this neglect the effect of interparticle interaction. In this thesis we investigate the effect of magnetic dipolar interaction in the magnetothermal efficiency (named specific loss power – SLP) of bicompatible magnetic nanoparticles. Firstly, we develop a chain of magnetic particles model, where we prove that the interaction leads to a contribution to the uniaxial anisotropy. This term in the free energy density allowed us to extract from the electron magnetic resonance technique (EMR) information about the mean chain size in the colloid. Further, this additional magnetic nanoparticle anisotropy term was used to develop an analytical theoretical model that takes into account the effect of the dipolar interaction between nanoparticles to SLP, considering the case where the magnetization responds linearly to the field (Linear Response Theory). Our calculations indicate that depending on the particle parameters, specially the anisotropy, the effect can be to enhance or decrease the heat generation. Moreover, we showed that increasing the chain size (number of particles in the chain) the optimal particle size for hyperthermia can decrease up to 30% in comparison with non-interacting particles. This result has several clinical implications, which allowed us to suggest some strategies for improving the therapeutic efficacy. In order to investigate experimentally the effect, two magnetic fluids, one containing spherical nanoparticles based on manganese ferrite (MnF-citrate) in the superparamagnetic regime, and another commercial one (BNF-starch) magnetite-based with a shape of a parallellepiped and blocked, were selected and deeply characterized. We found a decrease of SLP increasing the chain size for the MnF sample, while for BNF-starch no effect was found at the same experimental conditions. The decrease of SLP in the MnF sample, within the particle concentration range, was explained considering in the model not only the effect in the anisotropy but also by an increase in the damping factor parameter, a term correlated to spin-phonon interaction. Data obtained using EMR and Monte Carlo simulations corroborate our hypothesis. The absence of concentration effect for the BNF sample was attributed to the higher anisotropy value and to the probable influence of brownian relaxation. In addition, the same chain model was used to investigate the behavior of blocked nanoparticles of Stoner-Wohlfarth type. In this case, we demonstrate that the chain formation increases the magnetic hyperthermia, as found in magnetosomes. Finally, we showed that a fluctuation of the dipolar interaction field between particles in the chain, which does not destroy the symmetry of this term, shows a Vogel-Fulcher behaviour in the weak coupling regime.Item Hipertermia magnética in vivo com nanopartículas de MnFe2O4 no tratamento de tumores sólidos e subcutâneos de Sarcoma 180(Universidade Federal de Goiás, 2017-04-19) Rodrigues, Harley Fernandes; Lacerda, Elisângela de Paula Silveira; http://lattes.cnpq.br/9390789693192751; Bakuzis, Andris Figueiroa; http://lattes.cnpq.br/3477269475651042; Bakuzis, Andris Figueiroa; Lacerda, Elisângela de Paula Silveira; Silva, Carlos Jacinto da; Reis, Rui Manuel Vieira; Pontes, Renato BorgesIn this thesis a methodology of real-time monitoring of magnetic hyperthermia (HM) in vivo was developed in the murine tumor model Sarcoma 180 using infrared thermography technique. Magnetic nanoparticles (NPM) consisted of Mn ferrites capable of generating heat at low magnetic field amplitude at the 300 kHz frequency within the safety limit determined by Atkinson. It has been shown that the apparent surface temperature value measured with the infrared camera underestimates the real skin temperature value of the mice if the camera objective does not form an angle 0 ° with the normal direction to the animal's skin in the region of interest on the tumor, with the error reaching more than 7.0 ° C (for 60 °). A new theoretical model to estimate the error in the temperature of curved surfaces was developed and proved valid even in the case where the surface temperature diverges significantly from the environment. Preclinical treatment results indicated a complete remission condition in animal that was submitted to 150 min of hyperthermia and other cases with partial remission, suggesting that biological response analyzes need to be done in a long time (> 60 days). Measurements of the intratumoral temperature monitored by three fiber-optic thermometers during the therapeutic procedure of HM with NPM indicated an inhomogeneous heat delivery within the tumor. Additionally, a new methodology for calculating the thermal dose (CEM43) evaluated at the surface, considering each pixel of the thermographic image as a thermometer in the tumor region, indicated that the value T10(t) of the temperature detected in vivo at the surface of the skin over subcutaneous tumors can report, with an error of the order of 5%, the mean intratumoral temperature value during the therapeutic procedure of HM.Item Magnetohipertermia em nanopartículas core-shell(Universidade Federal de Goiás, 2016-05-04) Santos, Marcus Carrião dos; Bakuzis, Andris Figueiroa; http://lattes.cnpq.br/3477269475651042; Bakuzis, Andris Figueiroa; Knobel, Marcelo; Jadim, Renato de F.; Silva, Hermann F. F. Lima e; Pelegrini, FernandoThe 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.Item Construção, caracterização e otimização da magnetohipertermia de nanocarreadores multifuncionais fluorescentes: a importância da relaxação coletiva na geração de calor(Universidade Federal de Goiás, 2018-02-22) Zufelato, Nícholas; Bakuzis, Andris Figueiroa; http://lattes.cnpq.br/3477269475651042; Bakuzis, Andris Figueiroa; Nunes, Wallace de Castro; Silva, Sebastião William da; Pelegrini, Fernando; Bufaiçal, Leandro Felix de SousaIn this work, we developed a multifunctional nanocarrier that has diagnostics and therapeutic applications in oncology, and evaluated the magnetothermal efficiency (SLP) properties in a comparative manner with respect to magnetic fluids. The nanocarrier consists of Mn-ferrite magnetic nanoparticles, a near-infrared fluorescent molecule IR-780, that are surface-coated with albumin proteins (BSA). The samples were characterized by dynamic light scattering (DLS), electron microscopy (TEM and MEV-FEG), vibrating sample magnetometer (VSM), fluorescence molecular tomography (FMT). FMT data proved the coupling of IR-780 to the protein allowing the fabrication of a magnetofluorescent nanostructure. Magnetic hyperthermia data as function of field amplitude (60-200 Oe) and frequency (170-990 kHz) were obtained for all samples containing the same magnetic particle volume fraction in the liquid carrier, but with distinct agregate sizes. The sizes were controlled by tuning the ionic force, and monitored experimentally using DLS. Magnetization curves revealed a (quasi-static) superparamagneticlike behavior, and was used to extract the particle concentration. The hyperthermia efficiency SLP of the magnetic fluids decreased increasing the hidrodynamic diameter. On the contrary, the nanocarrier showed a maximum of SLP, that can be optimized for hyperthermia and is more efficient than the ferrofluid. SLP data as function of frequency revealed a relaxation time of the order of 10-7 s and an equilibrium susceptibility lower than the Langevin value. A theoretical analysis of SLP at the linear responde regime was developed taking into account the dipolar interaction of nanoparticles organized in distinct arrangements. In magnetic fluids we considered a linear chain using the longitudinal configuration (anisotropy axis aligned), while for the nanocarriers we considered spherical agregates where the anisotropy axis of the nanoparticles are arranged randomly. The theoretical analysis indicate that the relaxation time cannot be explained by brownian relaxation or the Néel relaxation of single particle (even considering the dipolar effect). But instead, a mechanism of collective relaxation, mediated by dipolar interaction, is responsible for heat generation. It also indicates that only a fraction of agregates in the colloid is responsible for heating. In addition, the theoretical model revealed the existence of a transition from single particle relaxation to collective relaxation only if the dipolar interaction for the aggregate is higher than a critical value, which depends on material parameters, as for instance anisotropy field and saturation magnetization. Indeed, the model indicates that collective states are more easily achieved on soft magnets, and therefore suggests enhanced magnetothermal properties for this kind of materials.