Nanoparticles and alloys for therapeutical and structural biomedical applications.

This thesis addresses 2 challenges in biomaterials research: 1) diffusion phenomena in Ti-Al-Nb alloys as materials for structural applications; and 2) the development of magnetic hyperthermia therapies against cancer more efficient and less invasive. Both challenges share a characteristic physical ground, which is the guideline of this work: they are based on transfer phenomena, mass transfer in the first case, and heat transfer in the second.Biomaterials research has been in an ascendant trend over the last decades. In biomedical applications, the first thing to be taken into consideration is biocompatibility. This property together with high specific strength, and good corrosion resistance has made titanium and its alloys the preferred materials for structural applications in the human body. Moreover, they have also been widely used in other fields like aerospace and marine industries. The composition of alloys is the most basic parameter that determines their properties. For instance, compared with the conventional Ti-6Al-4V alloy, some vanadium free titanium alloys like Ti-Al-Nb alloys, have higher fatigue strength, lower modulus of elasticity, and improved biocompatibility. All these properties are closely related to their microstructures that can be engineered by recovery, recrystallization, grain growth, transformation and precipitation. Furthermore, microstructural features can also be controlled to some extent by diffusion phenomena.Bibliometric studies show that in the uprising of Biomaterials research "Nanoparticles" has become the hottest topic after the turn of millennium. Indeed, nanotechnology, having been at the forefront of research for many years, has brought new genuine technical solutions in many different fields like biology, materials, electronics and medicine etc. One of the most exciting among them is that of therapeutical applications of nanoparticles (NPs), in which toxicity is also the main concern. For instance, in NP mediated magnetic hyperthermia for cancer therapy, only iron oxide nanoparticles (IONP), and particularly maghemite (-Fe2O3), are clinically accepted, in spite of existence of other materials like Co ferrite (CoFe2O4) that present clear advantages in terms of heating performance but show toxicity issues. Therefore, research efforts in this area have been mostly devoted to improve the performance of maghemite NPs by optimizing their structural parameters such as size, size distribution, shape, crystallinity, etc. There is however another polymorph of iron oxide, -Fe2O3, that has exceptional magnetic properties, but nevertheless has never been explored as a potential candidate for magnetic hyperthermia therapy.The idea of hyperthermia is to elevate the temperature of the tumor tissue over 42 ℃, in a selective way, to cause the apoptotic death of cancer cells. In order to heat selectively the tumor, it is peremptory to precisely monitor and control the temperature of the surrounding healthy tissue. Moreover, actual clinical magnetic hyperthermia technology uses massive direct injection of nanoparticles, which carries out some degree of invasiveness and toxicity issues. In order to avoid these problems and to expand the use of this technology in clinics, a new strategy has emerged that requires a reduced heat production. It is based on applying small amounts of heat but concentrated at certain intracellular regions that may lead to cancer cell apoptosis. To proof this hypothesis, it is first necessary to determine whether the heat produced by the MNPs is enough to generate large temperature gradients in small intracellular regions in the competition with heat dissipation process across the cell cytoplasm and then to the extracellular matrix. For this purpose, a non-invasive thermometric technique is required capable to determine local temperatures inside the cells with ultra-high spatial resolution. In this matter the use of lanthanide-based luminescent molecular thermometers can be a good option, as it will be shown in this thesis.This thesis is about: the diffusion phenomenon in the Ti-Al-Nb alloys, the hyperthermia performance of epsilon iron oxide nanoparticles, the fine-tuning of a ultra-high spatial and time resolution 2D temperature imaging system, the performance of Ln3+-bearing nanoparticles as nano-thermometry probes, obtaining intracellular temperature images, and the determination of temperature gradients in magnetic nanoparticles inside cancer cells under an ac magnetic field irradiation, and finally to investigate the validity of the local hyperthermia hypothesis.Chapter 1 will give a general introduction to the application of Titanium alloys and magnetic nanoparticles. The focus concerning titanium alloys will be put on diffusion phenomena, while in the case of magnetic nanoparticles, it will be mainly directed to magnetic hyperthermia and molecular nanothermometry.Chapter 2 contains the experimental section including methods, preparation and characterization of Titanium alloys, and magnetic and thermometric nanoparticle suspensions, and a description of the temperature imaging system.Chapter 3 is focused on diffusion phenomenon study of body centered cubic Ti-Al-Nb alloys by both experimental and computational methods, and the construction of a diffusion kinetic database. The experiments were conducted by the diffusion couple technique, and the computational work thereafter was accomplished by the DICTRA software.Chapter 4 and 5 demonstrates the hyperthermia performance of pure and Ga-doped epsilon iron oxide nanoparticles, in comparison with that of gamma iron oxide nanoparticles.Chapter 6 is dedicated to intracellular 2D temperature imaging and local magnetic hyperthermia by using Ln3+-bearing polymeric micelles.Chapter 7 is dedicated to the study of local hyperthermia by means of intracellular 2D temperature imaging of Ln3+-bearing iron oxide nanoparticles ac magnetic field application to cell cultures.<br /

Controlled release of bupivacaine using hybrid thermoresponsive nanoparticles activated via photothermal heating

Near-infrared (NIR) responsive nanoparticles are of great interest in the biomedical field as antennas for photothermal therapy and also as triggers for on-demand drug delivery. The present work reports the preparation of hollow gold nanoparticles (HGNPs) with plasmonic absorption in the NIR region covalently bound to a thermoresponsive polymeric shell that can be used as an on-demand drug delivery system for the release of analgesic drugs. The photothermal heating induced by the nanoparticles is able to produce the collapse of the polymeric shell thus generating the release of the local anesthetic bupivacaine in a spatiotemporally controlled way. Those HGNPs contain a 10 wt.% of polymer and present excellent reversible heating under NIR light excitation. Bupivacaine released at physiological temperature (37 °C) showed a pseudo-zero order release that could be spatiotemporally modified on-demand after applying several pulses of light/temperature above and below the lower critical solution temperature (LCST) of the polymeric shell. Furthermore, the nanomaterials obtained did not displayed detrimental effects on four mammalian cell lines at doses up to 0.2 mg/mL. From the results obtained it can be concluded than this type of hybrid thermoresponsive nanoparticle can be used as an externally activated on-demand drug delivery system

Development of new materials and techniques for luminescence nanothermometry and photothermal conversion

Hem estudiat la dependència amb la temperatura de la luminescència generada per nanopartícules dielèctriques dopades amb ions lantànids que poden ser utilitzades en nanotermometria luminescent. Hem analitzat nous materials amb emissió en el rang del visible de l’espectre electromagnètic, incloent Ho,Yb:KLu(WO4)2 i Ho,Tm,Yb:KLu(WO4)2, així com nanopartícules core-shell de Er,Yb:GdVO4@SiO2. També hem desenvolupat un nou mètode de síntesi solvotermal assistit per microones per nanopartícules de Er,Yb:NaYF4, que opera a temperatures més baixes i temps de reacció més curts que els mètodes convencionals. Hem utilitzat nanotermometria basada en la mesura dels temps de vida mitjana radiativa en nanopartícules up-conversores de Er,Yb:NaY2F5O per la determinació de temperatura en sistemes biològics, així com la determinació de temperatura pel canvi de color de l’emissió de nanopartícules de Tm,Yb:GdVO4@SiO2. Finalment, hem desenvolupat un sistema de nanotermometria luminescent simple i compacte que permetrà atansar la nanotermometria luminescent a l’entorn mèdic i industrial. Hem analitzat també la nanotermometria luminescent en la regió de l’infraroig proper. El Nd:KGd(WO4)2 mostra potencial com nanotermòmetre luminescent en aquesta regió per sistemes biològics, amb una profunditat de penetració d’1 cm en teixits biològics. Els ions Er3+ i Tm3+ mostren bandes d’emissió eficients en aquesta regió que poden utilitzar-se per nanotermometria luminescent en sistemes biològics. Les nanopartícules de Tm,Yb:GdVO4@SiO2, amb emissions localitzades en la primera finestra biològica, presenten una elevada sensitivitat tèrmica i s’han internalitzat en cèl·lules HeLa. Finalment, hem mostrat la multifuncionalitat de les nanopartícules de Ho,Tm:KLu(WO4)2 que actuen com nanotermòmetres, agents fototèrmics i marcadors biològics. També hem determinat l’eficiència de conversió fototèrmica del grafè i derivats, escalfadors eficients pel tractament de diverses malalties inclòs el càncer, i hem desenvolupat un nou mètode per determinar aquesta eficiència de conversió utilitzant una esfera integradora, un mètode que es pot estendre a altres agents fototèrmics.Hemos estudiado la dependencia con la temperatura de la luminiscencia generada por nanopartículas dieléctricas dopadas con iones lantánido que pueden ser usadas en nanotermometría luminiscente. Hemos analizado nuevos materiales con emisión en el rango del visible del espectro electromagnético, incluyendo Ho,Yb:KLu(WO4)2 y Ho,Tm,Yb:KLu(WO4)2, así como nanopartículas core-shell de Er,Yb:GdVO4@SiO2. También hemos desarrollado un nuevo método de síntesis solvotermal asistido por microondas para nanopartículas de Er,Yb:NaYF4, que opera a temperaturas más bajas y tiempos de reacción más cortos que los métodos convencionales. Hemos utilizado nanotermometría basada en la medida de tiempos de vida media radiativa en nanoparticulas up-conversoras de Er,Yb:NaY2F5O para la determinación de temperatura en sistemas biológicos, así como la determinación de temperatura por el cambio de color de la emisión de nanopartículas de Tm,Yb:GdVO4@SiO2. Finalmente, hemos desarrollado un sistema de nanotermometría luminiscente simple y compacto que va a permitir acercar la nanotermometría luminiscente al entorno médico e industrial. Hemos analizado también la nanotermometría luminiscente en la región del infrarojo cercano. El Nd:KGd(WO4)2 muestra potencial como nanotermómetro luminiscentes en esta región para sistemas biológicos, con una profundidad de penetración de 1 cm en tejidos biológicos. Los iones Er3+ y Tm3+ muestran bandas de emisión eficientes en esta región que pueden utilizarse para nanotermometría luminiscente en sistemas biológicos. Las nanopartículas de Tm,Yb:GdVO4@SiO2, con emisiones localizadas en la primera ventana biológica, presentan una elevada sensitividad térmica y se han internalizado en células HeLa. Finalmente, hemos mostrado la multifuncionalidad de las nanopartículas de Ho,Tm:KLu(WO4)2 que actúan como nanotermómetros, agentes fototérmicos y marcadores biológicos. También hemos determinado la eficiencia de conversión fototérmica del grafeno y derivados, calentadores eficientes para el tratamiento de diversas enfermedades incluido el cáncer, y hemos desarrollado un nuevo método para determinar esta eficiencia de conversión utilizando una esfera integradora, un método que puede extenderse a otros agentes fototérmicos.We studied the temperature dependence of the luminescence generated by dielectric nanoparticles doped with lanthanide ions to be used in luminescence nanothermometry. New materials emitting in the visible range of the electromagnetic spectrum, including Ho,Yb:KLu(WO4)2 and Ho,Tm,Yb:KLu(WO4)2 and Er,Yb:GdVO4@SiO2 core-shell nanoparticles have been analyzed for these purposes. Moreover, we developed a new and greener microwave-assisted solvothermal synthesis method for Er,Yb:NaYF4 nanoparticles that operates at lower temperatures and shorter reaction times than conventional methods. We used lifetime-based nanothermometry in upconversion Er,Yb:NaY2F5O nanoparticles for temperature determination in biological systems, and the change of color of the emission generated in Tm,Yb:GdVO4@SiO2 core-shell nanoparticles as a function of temperature. Furthermore, we developed a simple and compact setup that would approach luminescence nanothermometry to the real practical applications in medical and industrial environments. We also explored luminescence nanothermometry in the near infrared region of the electromagnetic spectrum. Nd3+-doped KGd(WO4)2 nanoparticles show potentiality as a luminescent nanothermometer in this region for biological systems, with a penetration depth of 1 cm in biological tissues. Er3+ and Tm3+ ions doped in different matrices have shown also efficient emission bands lying in the short-wavelength infrared region that can be used for luminescence thermometry in biological systems. Also, Tm3+,Yb3+:GdVO4@SiO2 core-shell nanoparticles with emissions located in the first biological window are presented as highly thermal sensitive nanothermometers and have been efficiently internalized in the HeLa cells. Finally, the multifunctionality of Ho3+ and Tm3+ co-doped KLu(WO4)2 nanoparticles has been shown, acting as nanothermometers, photothermal agents and biolabels for bioimaging. Also, we determined the photothermal conversion efficiency of graphene and graphene oxide, efficient heaters for the treatment of several diseases including cancer, and developed a new method for determining their photothermal conversion efficiency by using an integrating sphere, a method that can be extended to other photothermal agents

Synthesis and characterizations of multifunctional luminescent lanthanide doped materials

El desenvolupament de nanotermòmetres luminescents de no contacte basats en ions lantànids per ser utilitzats com a eines de diagnòstic precises, eficients i ràpides, propietats atribuïdes a la seva versatilitat, estabilitat i perfils de banda d'emissió estrets, ha portat cap a la substitució de les sondes tèrmiques de contacte convencionals. L'aplicació de nanopartícules dopades amb ions lantànids com nanosensors de temperatura, excitats amb llum ultraviolada, visible o infraroja propera, i la generació d'emissions en les regions espectrals de les finestres biològiques: I-BW (650 nm-950 nm), II-BW (1000 nm -1350 nm), III-BW (1400 nm-2000 nm) i IV-BW (centrada en 2200 nm), està creixent notablement a causa d’avantatges com la reducció de la fototoxicitat i el fotoblanqueig, un contrast d'imatge millor i una major profunditat de penetració en els teixits biològics. Entre aquestes finestres biològiques, la III-BW permet lectures tèrmiques més profundes dins de teixits biològics específics, atribuïdes a una major profunditat de penetració a causa de la reducció de l'absorbància i la dispersió en comparació amb les altres finestres biològiques. No obstant això, la termometria de luminescència en aquest règim espectral s'ha explorat poc. Aquí, hem sintetitzat i caracteritzat materials luminescents dopats amb Ho3+ i Tm3+ amb emissions ubicades a la III-BW per a la seva aplicació com a termòmetres luminescents i agents fototèrmics. Hem utilitzat partícules de KLu(WO4)2 i Y2O3 dopades amb Ho3+ i Tm3+ com a possibles agents fototèrmics automonitoritzats capaços d'alliberar calor i de determinar la temperatura simultàniament. Per a la seva síntesi, hem adaptat mètodes solvotermals (autoclau convencional i assistit per microones) i químics humits (descomposició tèrmica i maduració digestiva). Per acabar, hem aprofitat la peculiar configuració electrònica i les característiques morfològiques de les nanopartícules de Y2O3 per aplicar-les com a emissors de llum blanca i com a agents antioxidants ex vivo.El desarrollo de nanotermómetros luminiscentes de no contacto basados en iones lantánidos para ser usados como herramientas de diagnóstico precisas, eficientes y rápidas, propiedades atribuidas a su versatilidad, estabilidad y perfiles de banda de emisión estrechos, ha llevado a la sustitución de las sondas térmicas de contacto convencionales. La aplicación de nanopartículas dopadas con lantánidos como nanosensores de temperatura, excitados con luz ultravioleta, visible o infrarroja cercana, y la generación de emisiones en las regiones espectrales de las ventanas biológicas: I-BW (650 nm-950 nm), II-BW (1000 nm -1350 nm), III-BW (1400 nm-2000 nm) y IV-BW (centrada en 2200 nm), está creciendo notablemente debido a ventajas como la reducción de la fototoxicidad y el fotoblanqueo, un mejor contraste de imagen y una mayor profundidad de penetración en tejidos biológicos. Entre estas ventanas biológicas, la III-BW permite lecturas térmicas más profundas dentro de tejidos biológicos específicos, atribuidas a una mayor profundidad de penetración debido a la reducción de la absorbancia y la dispersión en comparación con las otras ventanas biológicas. Sin embargo, la termometría de luminiscencia en este régimen espectral se ha explorado poco. Aquí, hemos sintetizado y caracterizado materiales luminiscentes dopados con Ho3+ y Tm3+ con emisiones ubicadas en la III-BW para su aplicación como termómetros luminiscentes y agentes fototérmicos. Hemos utilizado partículas de KLu(WO4)2 y Y2O3 dopadas con Ho3+ y Tm3+ como posibles agentes fototérmicos automonitorizados capaces de liberar calor y determinar la temperatura simultáneamente. Para su síntesis, hemos adaptado métodos solvotermales (autoclave convencional y asistido por microondas) y químicos húmedos (descomposición térmica y maduración digestiva). Para finalizar, hemos aprovechado la peculiar configuración electrónica y las características morfológicas de las nanopartículas de Y2O3 para aplicarlas como emisores de luz blanca y como agentes antioxidantes ex vivo.The development of non-contact luminescent lanthanide nanothermometers as accurate, efficient and fast diagnostic tools, attributed to their versatility, stability and narrow emission band profiles, have led to the replacement of the conventional contact thermal probes. The application of lanthanide doped nanoparticles as temperature nanosensors, excited with ultraviolet, visible or near infrared light, and the generation of emissions lying in the biological windows spectral regions: I-BW (650 nm-950 nm), II-BW (1000 nm-1350 nm), III-BW (1400 nm-2000 nm) and IV-BW (centered at 2200 nm), is notably growing due to the advantages of reduced phototoxicity and photobleaching, better image contrast and deeper penetration depths into biological tissues. Among these biological windows, the III-BW allows for deeper thermal readings within specific biological tissues, attributed to a higher penetration depth due to the reduction of absorbance and scattering when compared to the other biological windows. Nevertheless, luminescence thermometry in this spectral regime is randomly explored. Here, we synthesized and characterized luminescent Ho3+ and Tm3+ doped materials with emissions located in the III-BW for their application as luminescent thermometers and photothermal agents. We explored Ho3+ and Tm3+ doped KLu(WO4)2 and Y2O3 particles as potential self-assessed photothermal agents able to release heat and determine temperature simultaneously. For their synthesis, we adapted solvothermal (microwave-assisted and conventional autoclave) and wet-chemical (thermal decomposition and digestive ripening) methods. To conclude, we took profit of the peculiar electronic configuration and morphological characteristics of the Y2O3 nanoparticles to apply them as white light emitters and as ex-vivo antioxidant agents

Nanopartículas contendo iões lantanídeos para termometria de luminescência

Doutoramento em FísicaA temperatura é uma variável chave que afeta a maior parte dos sistemas, quer naturais quer construídos pelo Homem. A medida da temperatura é global, uma vez que regula a cinética e a reatividade daqueles sistemas, ao nível atómico e macroscópico. Os sensores convencionais são ineficientes para a medição remota da temperatura à micro e à nanoescala o que, nos últimos anos, tem inspirado o desenvolvimento de nanotermómetros não-invasivos, sem contato, autorreferenciados e exibindo alta sensibilidade térmica. Neste contexto, a utilização de iões lantanídeos trivalentes (Ln3+), devido às suas propriedades fotoluminescentes que dependem fortemente da temperatura, tem sido uma das aproximações mais promissoras. Esta tese discuta as propriedades de nanopartículas dopadas com iões Ln3+ emitindo na gama espectral do visível e infravermelho-próximo como sensores de temperatura molecular. Na primeira parte da tese, estudaram-se nanopartículas de Gd2O3 dopadas com Nd3+ operando na gama espectral do infravermelho-próximo como nanotermómetros luminescentes baseados num rácio de intensidades. A emissão de nanotubos e nanobastonetes de Gd2O3:Nd3+ foi medida usando um tubo fotomultiplicador R928 comum na primeira janela biológica (800920 nm) tendo-se obtido na faixa fisiológica (288323 K), respetivamente, uma sensibilidade térmica e uma incerteza em temperatura de 1.75±0.04 %K-1 e 0.14±0.05 K. A dependência com a temperatura da emissão de nanoesferas de Gd2O3:Nd3+ na segunda janela biológica (12501550 nm), com excitação a 808 nm na primeira janela biológica, foi, também, estudada mostrando uma sensibilidade térmica máxima de 0.237±0.03 %K-1 a 303 K. Na segunda parte da tese foram desenvolvidas nanopartículas conversoras ascendentes de energia de Gd2O3 e SrF2 dopadas com Yb3+/Er3+ para termometria, tendo como parâmetro termométrico a intensidade integrada das transições 2H11/24I15/2/4S3/24I15/2 do ião Er3+. Desenvolveram-se nanoplataformas combinando nanotermómetros de Gd2O3:Yb3+/Er3+ com nanopartículas de Ouro (nanoaquecedores) para medir a temperatura induzida pelo plasmão das partículas metálicas. A condição ótima para um aquecimento térmico efetivo foi conseguida ajustando a banda de ressonância de superfície localizada do plasmão (LSPR) na gama fisiológica (302330 K). Quando comparadas com as nanopartículas de Gd2O3:Yb3+/Er3+, as nanopartículas de SrF2:Yb3+/Er3+ apresentam uma eficiência de emissão da conversão ascendente de energia e uma dispersibilidade superiores tendo sido estudada a dependência com a temperatura das suas propriedades de emissão, tanto em forma de suspensão como em pó. Além disso, realizaram-se medições do fluxo espectral e do rendimento quântico absoluto de emissão usando um espectrômetro com uma esfera de integração e um medidor de potência. Foi, também, proposto um método inovador para prever a curva de calibração da intensidade de emissão versus temperatura de qualquer termómetro luminescente baseado em dois níveis eletrónicos termicamente acoplados, utilizando como exemplo nanopartículas de SrF2:Yb3+/Er3+.Temperature is a master variable that affects essentially most of the natural and engineered systems. The measurement of temperature is a virtually ubiquitous requirement as it governs the kinetics and reactivity of these systems from their atomic to macroscopic level. The conventional temperature sensors, proved to be ineffective for remote temperature measurement at the micro and nanoscale. This has been strongly stimulated for the development of non-invasive, noncontact and self-referencing nanothermometers exhibiting high thermal sensitivity. In this context one of the most promising approaches proposes the use of trivalent lanthanide ions (Ln3+) that present photoluminescent properties that are temperature dependent. This thesis reports Ln3+-doped visible emitting upconverting and near-infrared emitting downshifting nanoparticles as molecular temperature sensors. Primarily, Nd3+-doped near-infrared exciting and near-infrared emitting downshifting Gd2O3 nanoparticles as an intensity-based ratiometric nanothermometer were evaluated. The performance of Gd2O3:Nd3+ nanorods were enquired using a common R928 photomultiplier tube in the first transparent biological window (800–920 nm). The highest thermal sensitivity and temperature uncertainty (1.75±0.04 %K−1 and 0.14±0.05 K, respectively) were reported for Gd2O3:Nd3+ nanorods in the physiological range (288–323 K). Similarly, the performance of Gd2O3:Nd3+ nanospheres were briefly investigated for their temperature dependent emission in the second biological window (12501550 nm) upon excitation in the first biological window (at 808 nm). The Gd2O3:Nd3+ nanospheres exhibit a maximum thermal sensitivity of 0.237±0.03 %K-1 at 303 K were obtained. Secondarily, Yb3+/Er3+-doped near-infrared exciting and visible emitting upconverting Gd2O3 and SrF2 nanoparticles were developed for thermometry based on the thermometric parameter, as the integrated intensity of 2H11/2→4I15/2/4S3/2→4I15/2 Er3+ transitions. Gd2O3 nanorods as thermometers combined with Au as heater nanoplatforms were constructed, to measure plasmon-induced temperature increase of Au nanorods. The optimal condition for the effective thermal heating was achieved by tuning the localized surface plasmon resonance band in the physiological range (302–330 K). In order to increase upconversion emission efficiency and the dispersibility, further SrF2 nanoparticles were explored and the thermal sensing properties were exploited both in powder and water suspension forms. Moreover, the measurements of spectral flux and the absolute quantum yield were accomplished followed a method using an integrating sphere-based spectrometer and a power meter. Considered a furtherance step is to demonstrate a straightforward method to predict the temperature calibration curve of any upconverting thermometer based on two thermally-coupled electronic levels independently of the medium, taking SrF2 nanoparticles as an illustrative example

Is a Quantum Biosensing Revolution Approaching? Perspectives in NV‐Assisted Current and Thermal Biosensing in Living Cells

none8openPetrini, Giulia; Moreva, Ekaterina; Bernardi, Ettore; Traina, Paolo; Tomagra, Giulia; Carabelli, Valentina; Degiovanni, Ivo Pietro; Genovese, MarcoPetrini, Giulia; Moreva, Ekaterina; Bernardi, Ettore; Traina, Paolo; Tomagra, Giulia; Carabelli, Valentina; Degiovanni, Ivo Pietro; Genovese, Marc

Ag2S nanodots for advanced biological applications through Luminescence Thermometry and Fluorescence Images .

Tesis doctoral inédita cotutelada por la Universidade Federal de Alagoas de Brasil y la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Física de Materiales. Fecha de lectura: 13-03-202

Multifunctional nanoparticles for hyperthermia, thermometry and fluorescenceimaging in the biological windows

Tesis Doctoral inédita cotutelada por la Universidade Federal de Alagoas de Brasil y la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Física de Materiales. Fecha de lectura: 17-12-2018In this thesis, the use of core/shell engineering for the synthesis of fluorescent nanoparticles (NPs) capable of operating as nanothermometers, nanoheaters and/or contrast agents for fluorescence imaging in small animal models is explored. The materials here studied – rare-earth (Nd3+, Yb3+, Tm3+ and/or Er3+) doped NPs and PbS/CdS/ZnS quantum dots (QDs) – presented emission and/or excitation bands in the so-called biological windows, where light penetration into tissues is maximal, allowing for ex vivo and in vivo applications. It was demonstrated that the spatial separation between the rare-earth ions, achieved by the core/shell nano-engineering, resulted not only in a considerable improvement on the values of thermo-optical parameters such as the light-heat conversion efficiency and the relative thermal sensitivity, but also on a multi-functionality of the nanosystems. As a consequence, innovative applications in nanothermometry were successfully accomplished when developing this thesis. Among those applications, one can mention: the study in real time of the thermal dynamics of an in vivo tissue, the detection and monitoring of cardiovascular diseases and the recording of in vivo thermal images and videos at a subcutaneous level by means of a ratiometric approach. The results here presented open up avenues for new diagnosis and control techniques that can revolutionize the current methods found in biomedicin