A method to obtain the thermal parameters and the photothermal transduction efficiency in an optical hyperthermia device based on laser irradiation of gold nanoparticles

Optical hyperthermia systems based on the laser irradiation of gold nanorods seem to be a promising tool in the development of therapies against cancer. After a proof of concept in which the authors demonstrated the efficiency of this kind of systems, a modeling process based on an equivalent thermal-electric circuit has been carried out to determine the thermal parameters of the system and an energy balance obtained from the time-dependent heating and cooling temperature curves of the irradiated samples in order to obtain the photothermal transduction efficiency. By knowing this parameter, it is possible to increase the effectiveness of the treatments, thanks to the possibility of predicting the response of the device depending on the working configuration. As an example, the thermal behavior of two different kinds of nanoparticles is compared. The results show that, under identical conditions, the use of PEGylated gold nanorods allows for a more efficient heating compared with bare nanorods, and therefore, it results in a more effective therapy.

Self-organized colloidal quantum dots and metal nanoparticles for plasmon-enhanced intermediate-band solar cells

A colloidal deposition technique is presented to construct long-range ordered hybrid arrays of self-assembled quantum dots and metal nanoparticles. Quantum dots are promising for novel opto-electronic devices but, in most cases, their optical transitions of interest lack sufficient light absorption to provide a significant impact in their implementation. A potential solution is to couple the dots with localized plasmons in metal nanoparticles. The extreme confinement of light in the near-field produced by the nanoparticles can potentially boost the absorption in the quantum dots by up to two orders of magnitude. In this work, light extinction measurements are employed to probe the plasmon resonance of spherical gold nanoparticles in lead sulfide colloidal quantum dots and amorphous silicon thin-films. Mie theory computations are used to analyze the experimental results and determine the absorption enhancement that can be generated by the highly intense near-field produced in the vicinity of the gold nanoparticles at their surface plasmon resonance. The results presented here are of interest for the development of plasmon-enhanced colloidal nanostructured photovoltaic materials, such as colloidal quantum dot intermediate-band solar cells.

Contribución al estudio de sistemas de hipertermia óptica y su aplicación en muestras biológicas

Las nanopartículas de metales nobles (especialmente las de oro) tienen un gran potencial asociado al desarrollo de sistemas de terapia contra el cáncer debido principalmente a sus propiedades ópticas, ya que cuando son irradiadas con un haz de luz sintonizado en longitud de onda con su máximo de Resonancia de Plasmón Superficial, absorben de manera muy eficiente dicha luz y la disipan rápidamente al medio en forma de calor localizado. Esta característica por tanto, puede ser aprovechada para conseguir elevar la temperatura de células tumorales hasta sobrepasar umbrales a partir de los cuales se produciría la muerte celular. Partiendo de estos principios, esta tesis se centra en el desarrollo y la caracterización de una serie de prototipos de hipertermia óptica basados en la irradiación de nanopartículas de oro con un haz de luz adecuado, así como en la aplicación in vitro de la terapia sobre células cancerígenas. Además, el trabajo se orienta a identificar y comprender los procesos mecánicos y térmicos asociados a este tipo de hipertermia, y a desarrollar modelos que los describan, estudiando y planteando nuevas formas de irradiación, para, en última instancia, poder optimizar los procesos descritos y hacerlos más efectivos. Los resultados obtenidos indican que, el uso de nanopartículas de oro, y más concretamente de nanorods de oro, para llevar a cabo terapias de hipertermia óptica, permite desarrollar terapias muy efectivas para inducir muerte en células cancerígenas, especialmente en tumores superficiales, o como complemento quirúrgico en tumores internos. Sin embargo, los efectos de la toxicidad de las nanopartículas de oro, aún deben ser detalladamente estudiados, ya que este tipo de terapias sólo será viable si se consigue una completa biocompatibilidad. Por otro lado, el estudio exhaustivo de los procesos térmicos que tienen lugar durante la irradiación de las nanopartículas ha dado lugar a una serie de modelos que permiten determinar la efectividad fototérmica de las nanopartículas y además, visualizar la evolución de la temperatura tanto a escala nanométrica como a escala macrométrica, en función de los parámetros ópticos y térmicos del sistema. El planteamiento de nuevas formas de irradiación y el desarrollo de dispositivos orientados a estudiar los fenómenos mecánicos que tienen lugar durante la irradiación pulsada de baja frecuencia y baja potencia de nanopartículas de oro, ha dado lugar a la detección de ondas de presión asociadas a procesos de expansión termoelástica, abriendo la puerta al desarrollo de terapias de hipertermia que combinen la muerte celular producida por calentamiento con la muerte derivada de los fenómenos mecánicos descritos.VII Noble metal nanoparticles (especially gold ones), have a huge potential in the development of therapy systems against cancer mainly due to their optical properties, so that, when these particles are irradiated with a light that is syntonized in wavelength with their maximum of Surface Plasmon Resonance, they effectively absorb and dissipate the light to the surrounding medium as localized heat. We can take advantage of this characteristic for rising the temperature of cancer cells above the threshold at which cellular death would occur. From these principles, this thesis is oriented to the development and characterization of a series of optical hyperthermia prototypes based on the irradiation of gold nanoparticles using the suitable light, and on the in vitro application of this therapy over cancer cells, to understand the mechanical and thermal processes associated with this kind of hyperthermia, developing descriptive models, and to study and to approach new ways of irradiation in order to, ultimately, optimize the described processes and make them more effective. The obtained results show that, the use of gold nanoparticles, and more specifically, of gold nanorods, to carry out optical hyperthermia therapies, allows the development of very effective therapies in order to induce death in VIII cancer cells, especially in superficial tumors, or like surgical complement in more internal tumors. However, the toxicity effects of the gold nanoparticles still need to be studied more detail, because this kind of therapies will be feasible only if a complete biocompatibility is achieved. On the other hand, the exhaustive study of the thermal processes that take place during the irradiation of the nanoparticles resulted in a series of models that allow the determination of the photothermal efficiency of the nanoparticles and also the visualization of the temperature evolution, both at nanoscale and at macroscale, as a function of the optical and thermal parameters of the system. The proposal of new ways of irradiation and the development of devices oriented to study the mechanical effects that take place during the low frequency and low power pulsing irradiation of gold nanoparticles has led to the detection of pressure waves associated to thermoelastic expansion processes, opening the door to the development of hyperthermia therapies that combine the cellular death due to the heating with the death derived from the described mechanical phenomena.

Caracterización de nanopartículas magnéticas y de oro para posibles aplicaciones biomédicas en diagnóstico y terapia

Los nanomateriales han adquirido recientemente un gran interés debido a la gran variedad de aplicaciones que pueden llegar a tener en el ámbito de la biomedicina. Este trabajo recoge las posibilidades tanto diagnósticas como terapéuticas que presentan dos modalidades de nanomateriales: nanopartículas de óxido de hierro y nanopartículas de oro. Para ello, en una primera aproximación se ha llevado a cabo la caracterización de las nanopartículas desde el punto de vista de la biocompatibilidad asociada a su tamaño y al tiempo de contacto o circulación en células y tejidos, ensayada tanto in vitro como in vivo así como la cinética de acumulación de dichas nanopartículas en el organismo vivo. Posteriormente se ha realizado la biofuncionalización de los dos tipos de nanopartículas para reconocer dianas moleculares específicas y poder ser utilizadas en el futuro en dos aplicaciones biomédicas diferentes: diagnóstico de enfermedad de Alzheimer mediante imagen de resonancia magnética y destrucción selectiva de células tumorales mediante hipertermia óptica. ABSTRACT Nanomaterials have recently gained a great interest due to the variety of applications that can have in the field of biomedicine. This work covers both diagnostic and therapeutic possibilities that present two types of nanomaterials: iron oxide nanoparticles and gold nanoparticles. Therefore, in a first approximation it has performed the characterizing of nanoparticles from the standpoint of biocompatibility associated with their size and time of contact or movement in cells and tissues, tested both in vitro and in vivo as well as the kinetics of accumulation of the nanoparticles into the living organism. Subsequently the biofunctionalization of two types of nanoparticles was made to recognize specific molecular targets and can be used in the future in two different biomedical applications: diagnosis of Alzheimer's disease by magnetic resonance imaging and selective destruction of tumor cells by optical hyperthermia.

Evaluation of the bioaccumulation kinetics of gold nanorods in vital mammalian organs by mean of TXRF spectrometry

This work presents the first application of total-reflection X-ray fluorescence (TXRF) spectrometry, a new and powerful alternative analytical method, to evaluation of the bioaccumulation kinetics of gold nanorods (GNRs) in various tissues upon intravenous administration in mice. The analytical parameters for developed methodology by TXRF were evaluated by means of the parallel analysis of bovine liver certified reference material samples (BCR-185R) doped with 10 μg/g gold. The average values (n = 5) achieved for gold measurements in lyophilized tissue weight were as follows: recovery 99.7%, expanded uncertainty (k = 2) 7%, repeatability 1.7%, detection limit 112 ng/g, and quantification limit 370 ng/g. The GNR bioaccumulation kinetics was analyzed in several vital mammalian organs such as liver, spleen, brain, and lung at different times. Additionally, urine samples were analyzed to study the kinetics of elimination of the GNRs by this excretion route. The main achievement was clearly differentiating two kinds of behaviors. GNRs were quickly bioaccumulated by highly vascular filtration organs such as liver and spleen, while GNRs do not show a bioaccumulation rates in brain and lung for the period of time investigated. In parallel, urine also shows a lack of GNR accumulation. TXRF has proven to be a powerful, versatile, and precise analytical technique for the evaluation of GNRs content in biological systems and, in a more general way, for any kind of metallic nanoparticles.