Valdés, Daniela Paola (2024) Hipertermia de nanopartículas magnéticas en fantomas: de la teoría al experimento / Hyperthermia of magnetic nanoparticles in phantoms: from the theory to the experiment. Tesis Doctoral en Física, Universidad Nacional de Cuyo, Instituto Balseiro.
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Resumen en español
Los tratamientos médicos contra el cáncer basados en nanopartículas, como la hipertermia magnética, son ampliamente investigados en la actualidad. Sin embargo, hay numerosos factores que dificultan su predictibilidad, reproducibilidad y la interpretación de los experimentos (en términos de incremento de temperatura o absorción de potencia) cuando son llevados a cabo en sistemas in vitro o in vivo. Algunos de ellos son la influencia de la viscosidad del medio y los efectos de interacciones debido a la aglomeración de las nanopartículas. Esto nos conduce a tratar de entender como se comportan los sistemas no ideales que poseen distribuciones de parámetros intrínsecos a las nanopartículas, as como a estudiar las distribuciones de temperatura durante el calentamiento de la muestra. El objetivo de esta tesis es abordar estos problemas a través de una retroalimentación entre enfoques teóricos y experimentales. Comenzamos por generar un marco teórico que nos permite entender como se comportan magnéticamente sistemas de nanopartículas simples (tanto no interactuantes como cadenas unidimensionales ideales), el rol de diferentes parámetros en la relajación magnética y explicar como el mismo agregado en diferentes condiciones experimentales puede tener un efecto beneficioso o perjudicial en la absorción de potencia. Con este marco teórico a mano, preparamos sistemas de características controladas que obran de fantomas celulares. Estos consisten de nanopartículas fijas en una matriz de gel, tanto dispersas como formando agregados. Mediante una caracterización exhaustiva de las nanopartículas y de los fantomas, que incluye tanto estudios de microscopía como mediciones magnéticas, recolectamos información sobre su morfología, composición y comportamiento magnético en condiciones dc y ac. Para comprender los resultados de magnetometría ac en condiciones típicas de hipertermia, modelamos sistemas similares a los reales, con distribuciones de tamaño, anisótropa y diferentes grados de aglomeración, tanto de manera analítica como efectiva. Finalmente, volvemos a poner el foco sobre la medición y desarrollamos un método de análisis que permite obtener mapas de evolución del incremento de temperatura durante experimentos de hipertermia para diferentes puntos en los fantomas, de manera simultanea y no invasiva. El mismo consiste en la adquisición de vídeos a través de una cámara termográfica y su posterior procesamiento. En contraste con las mediciones convencionales con sonda local, permite evaluar distribuciones de temperatura as como flujo de calor, potencia y da idea de las perdidas térmicas, lo cual es esencial para el entendimiento de experimentos in vitro, in vivo y de futuros tratamientos debido a la complejidad que introduce la perfusión sanguínea y las condiciones tumorales en la interpretación de los resultados. El desarrollo de este trabajo de tesis, en el cual los aspectos teóricos y experimentales se han alternado y retroalimentado a lo largo del mismo, nos ha permitido captar los factores físicos mas relevantes en los experimentos de hipertermia magnética abordados. Para resumir, llevamos a cabo exitosamente la síntesis y caracterización de tres muestras, logrando controlar sus propiedades morfológicas y magnéticas, as como obtener detalles de su composición. Con ellas, preparamos fantomas celulares en los cuales pudimos obtener aglomerados elongados de partículas mediante campos magnéticos ac típicos de experimentos de hipertermia. Los fantomas se caracterizaron extensivamente y se evaluó su absorción de potencia mediante métodos magnéticos (ciclos ac) y calorimétricos (estudios con cámara termográfica). Para reproducir estos ciclos ac mediante simulaciones, nos nutrimos de la información obtenida mediante la caracterización previa de los fantomas para desarrollar un modelo efectivo que mantiene los elementos esenciales para determinar su comportamiento magnético en estas condiciones. Desarrollamos, a partir de las medidas con la cámara termográfica, un método con mucha potencialidad para estudiar dinámica de calentamiento y distribuciones heterogéneas de nanopartículas en una matriz, con capacidad de análisis 2D que demuestra ser muy superior a las mediciones con sonda local. Este enfoque global sobre la hipertermia magnética abre el camino para nuevos estudios de sistemas de nanopartículas complejos utilizados en la aplicación.
Resumen en inglés
Medical cancer treatments based on nanoparticles such as magnetic hyperthermia are widely investigated nowadays. However, there are numerous factors that hinder the predictability, reproducibility and interpretation of the experiments (in terms of temperature increase or power absorption) when they are carried out in vitro or in vivo. Some of them are the influence of the medium's viscosity and the effects of interactions due to nanoparticle agglomeration. This leads us to try to understand how non-ideal systems with distributions of nanoparticle-intrinsic parameters behave, as well as to study temperature distributions during sample heating. The goal of this thesis is to address these problems through a feedback loop between theoretical and experimental approaches. We begin by generating a theoretical framework that allow us to understand how simple nanoparticle systems behave magnetically (both non-interacting and ideal one-dimensional chains), the role of different parameters in magnetic relaxation and explain how the same aggregate in different experimental conditions can have a beneficial or detrimental effect on power absorption. With this theoretical framework at hand, we prepare systems with controlled characteristics which act as cellular phantoms. They consist of nanoparticles fixed into a gel matrix, both dispersed and forming aggregates. Through a comprehensive characterization of the nanoparticles and phantoms, including both microscopy studies and magnetic measurements, we collect information on their morphology, composition, and magnetic behavior under dc and ac conditions. To understand the results of ac magnetometry under typical hyperthermia conditions, we model systems similar to real ones, with size distributions, anisotropy and different degrees of agglomeration, both analytically and effectively. Finally, we return our focus to the measurements and develop an analysis method that allows us to obtain temperature-evolution maps during hyperthermia experiments for different points on the phantoms, simultaneously and non-invasively. It consists of video acquisition through a thermographical camera and its subsequent processing. In contrast to conventional measurements with local probes, it allows to evaluate temperature distributions as well as heat flow, power and addresses thermal losses, which is essential for the understanding of in vitro and in vivo experiments, as well as future treatments due to the complexity introduced into the system by blood perfusion and tumoral conditions, making it more dificult to interpret results. The development of this thesis work, in which we have alternated between the theoretical and experimental aspects and worked with their feedback throughout, has allowed us to capture the most relevant physical factors in the magnetic hyperthermia experiments addressed. To summarize, we successfully carried out the synthesis and characterization of three samples, managing to control their morphological and magnetic properties, as well as get details of their composition. With them, we prepared cell phantoms in which we were able to obtain elongated agglomerates of particles using ac magnetic fields typical of hyperthermia experiments. The phantoms were extensively characterized and their power absorption was evaluated using magnetic (ac loops) and calorimetric (thermographic camera studies) methods. To reproduce these ac loops through simulations, we draw on the information obtained through the previous characterization of the phantoms to develop an effective model that maintains the essential elements to determine their magnetic behavior under these conditions. We developed, based on measurements with the thermographic camera, a method with great potential to study heating dynamics and heterogeneous distributions of nanoparticles in a matrix, with 2D-analysis capacity that proves to be much superior to measurements performed with local probes. This comprehensive approach to magnetic hyperthermia opens the way for new studies of complex nanoparticle systems used in the application.
| Tipo de objeto: | Tesis (Tesis Doctoral en Física) |
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| Palabras Clave: | Nanoparticles; Nanopartículas; Thermography; Termografía; Phantoms; Anisotropy; Anisotropía; Hysteresis; Histéresis; [Magnetic hyperthermia; Hipertermia magnética; Fantomas] |
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| Materias: | Física |
| Divisiones: | Investigación y aplicaciones no nucleares > Física > Resonancias magnéticas |
| Código ID: | 1267 |
| Depositado Por: | Tamara Cárcamo |
| Depositado En: | 12 Sep 2024 11:15 |
| Última Modificación: | 12 Sep 2024 11:15 |
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