Resumen de Synthesis and characterizations of multifunctional luminescent lanthanide doped materials
The development of luminescence nanothermometers with accurate, remote, and all-optically-based thermal sensing capacities have led to the replacement of the conventional contact thermal probes. Among the different classes of luminescence nanothermometers, lanthanide based materials have emerged as a promising choice due to their peculiar electronic configuration. Lanthanide ions exhibit sharp emission lines, are photochemically stable, barely non-toxic, and display no photobleaching effect when excited with the suitable energy source. In addition, these materials can operate in a very broad range of the electromagnetic spectrum, covering from the ultraviolet to the near infrared, depending on the ion chosen, and only limited by the transparency of the host in which they are embedded.
The interest for lanthanide ions whose emissions are located within the so-called biological windows, is continuously growing due to the advantages of getting better image contrast and deeper penetration depths into biological tissues. Biological windows portray the spectral ranges where biological tissues become partially transparent due to a simultaneous reduction in both absorption and scattering of light. There have been defined four types of biological windows: 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). The applicability of lanthanide nanothermometers has been mainly limited up to now to materials operating within the I- and II-BWs. Nevertheless, it has been demonstrated that the scattering coefficient decreases when the wavelength increases into the near-infrared, and light in the III-BW transmits up to three times more efficiently through specific biological tissues, like those containing melanine, achieving higher light penetration depths. This would allow for deeper temperature sensing, although scarcely explored to date.
Triggered by the advantages that the III-BW can offer, we opted for the preparation of lanthanide doped particles of yttrium oxide (Y2O3) and potassium lutetium tungstate (KLu(WO4)2 for luminescence nanothermometry purposes in the III-BW. We selected Ho3+ and Tm3+ as lanthanide emitters. These two ions, first, have emissions located in the III-BW, mainly at 1.4 μm and 1.8 μm in the case of Tm3+, and at 1.96 μm in the case of Ho3+. Second, these emissions can be achieved by exciting the materials with low-cost near infrared light sources, and they do not suffer from photobleaching, autofluorescence and photoxicity upon biological matter when compared to the commonly used ultraviolet sources. In addition, this light source allows for deep-tissue penetration within the biological windows regimes when compared to the commonly used visible sources. Furthermore, Ho3+ and Tm3+ ions, upon near infrared excitation, can simultaneously generate light and heat, due to the radiative and non-radiative processes that can happen in their electronic structure. In this way, these materials can act as self-assessed photothermal agents, in which the same particle releases heat and emit light that allows determining the temperature in situ. In terms of the host where these lanthanide ions are embedded, it is important to underlie that the host should offer a high chemical stability, large values of absorption and emission cross sections for lanthanide ions, and the possibility to dope the material, regardless of the concentration level, without fluorescence quenching. These properties can be encountered in simple cubic rare-earth oxides (RE2O3, RE = rare-earth) or monoclinic double tungstates (KRE(WO4)2).
For Ho3+ and Tm3+ doped KLu(WO4)2 particles, we optimized the concentration of these doping ions to maximize their performance as self-assessed photothermal agents when synthesized through the well-established modified sol-gel Pechini method. The results revealed that a dopant concentration of 3 mol% Ho3+ and 5 mol% Tm3+ generated the brightest emissions in the III-BW, whereas a dopant concentration of 1 mol% Ho3+ and 10 mol% Tm3+ exhibited the best self-assessed photothermal properties within the physiological range of temperatures. Nevertheless, this synthesis method, based on the formation of organic-inorganic composite materials, formed at relative low temperatures by the hydrolysis of the constituent molecular precursors, a subsequent polycondensation, and a last process of calcination at 1073 K, suffers from morphological irregularities and wide size particles distribution up to several microns.
To overcome these drawbacks, we studied how microwave-assisted (MW) and conventional autoclave (CA) solvothermal methods, in the presence of organic surfactants such as oleic acid (OLAC) and oleylamine (OLAM), can allow obtaining more regular nanoparticles with a smaller size dispersion. The organic surfactants chosen have the ability to be selectively attached to a certain crystallographic plane of the product, controlling its nucleation and growth. The final products of these reactions resulted to be monoclinic KLu(WO4)2 nanoparticles with a close-to-spherical shape and sizes below 20 nm, with no tendency to agglomeration.
Still, the morphological characteristics of these particles were not properly defined. Thus, we studied the opportunity to develop the synthesis of these particles via wet-chemical methods. We opted for thermal decomposition reactions, in which the precursors were added into a mixture of organic surfactants, mainly OLAC, OLAM and 1-octadecene (ODE), and the whole mixture was treated under vacuum and protective nitrogen atmosphere. The final product was confirmed structurally to belong to the monoclinic KLu(WO4)2. TEM images, revealed well-defined rod shaped particles with sizes around 1 μm in length and 180 nm in width.
Comparing the self-assessed photothermal properties of these different Ho3+ and Tm3+ doped KLu(WO4)2 particles within the physiological range of temperatures, the results underlined the significant role of the size and shape of the particles. Hence, in terms of thermal sensing, the particles synthesized by the modified sol-gel Pechini methodology, sense temperature better, whereas for the ability to transform the absorbed light into heat, the well-defined rod shaped particles obtained by the thermal decomposition method, generate 66% heat, a value up to 2 times higher when compared to the other Ho3+ and Tm3+ doped KLu(WO4)2 nanoparticles, and comparable to that obtained with gold nanoparticles. On the other hand, the small particles synthesized by the solvothermal methods are stable in aqueous solutions for 4.5 h, rendering these particles as potential candidates for sensing temperature within biological media, regardless of their lower temperature sensing abilities. Because of their higher thermal sensitivity, we applied the 1 mol% Ho3+ and 10 mol% Tm3+ doped KLu(WO4)2 particles, synthesized by the sol-gel Pechini methodology as ex-vivo self-assessed photothermal agents that could sense the temperature with a difference of only 0.8 K to respect that measured with a control thermocouple located near the nanoparticles.
Concerning Y2O3, it crystallized in the cubic system and presents a very broad transparency range (0.2-8 μm), a large band gap (5.6 eV), a high thermal conductivity, a high refractive index, and a low phonon energy So, it is an attractive choice as host material for Ho3+ and Tm3+ for luminescent applications. Here, we prepared yttria colloidal nanocrystals with diverse sizes and shapes by applying wet chemical methods. We synthesized nanotriangles and nanohearts with sizes ~44 nm and ~53 nm, respectively, by applying a thermal decomposition method and tuning the reaction time. In addition, yttria self-assembled nanodiscs (diameter ~21 nm and thicknesses of the order of the dimensions of the unit cell) were obtained by applying a digestive ripening method, in which OLAC was swiftly injected into a solution containing OLAM and the lanthanide precursors. These yttria colloidal nanocrystals were tested as potential luminescent nanothermometers and photothermal conversion agents, operating in the III-BW. The generated photoluminescence in these colloidal nanocrystals, after excitation with NIR light, included three bands attributed to the electronic transitions: 3H4-3F4 (1.5 µm) and 3F4-3H6 (1.85 µm, composed by two Stark sublevels with emissions lying at 1.8 µm and 1.96 µm) of Tm3+, and 5I7- 5I8 (2.1 µm) of Ho3+, slightly shifted when compared to the position of the emission bands observed in Ho3+ and Tm3+ doped KLu(WO4)2 materials. In terms of temperature sensing abilities, a relationship between the size of the nanocrystals and their performance as nanothermometers could be extracted: the smaller the size, the higher the thermal sensitivity. Concerning the ability to generate heat, the best light-to-heat conversion efficiency was obtained for the nanotriangles with a value of 15 ± 2 %. We also explored more sophisticated nanoarchitectural structures, by preparing core@shell and layer-by-layer structures based on the nanotriangles as seed precursors, added at room temperature and at the crystallization temperature, respectively. These nanoarchitectures improve the brightness of the emissions and the photothermal conversion efficiency, nevertheless, the temperature sensing properties are not enhanced.
A part from the temperature sensing in the III-BW, we explored other applications for the yttria nanocrystals. Upon excitation with high power NIR light, yttria nanotriangles generated white light.
We investigated the effects of the generation of this white light on the crystalline structure, size, shape, and surface chemistry of these nanoparticles. In addition, the influence of factors like the excitation laser power, illumination time, and temperature at which the colloidal nanocrystals were exposed, were analyzed. The emission depended highly on the temperature, which allowed us to apply these materials as visible luminescent nanothermometers, probing a novel scheme for temperature sensing. Finally, we explored the application of yttria nanocrystals as potential antioxidant therapeutic agents. These nanoparticles, due to their non-stoichiometric characteristics, can prevent the generation of harmful hydroxyl radical species. We analyzed the antioxidant properties in yttria nanocrystals nanotriangles, nanohearts and nanodiscs, by applying a Fenton reaction in the presence of methyl violet as chromogenic agent. Further, the effect of dopants on their antioxidant properties, incorporated in yttrium oxide host, was explored. The results indicate that these nanoparticles exhibit antioxidant properties at the same level than ceria nanoparticles, much more explored for this application. These antioxidant properties were also tested in an ex-vivo experiment checking the reaction between the catalase of liver and H2O2, and concluding that these particles can prevent the formation of hydroxyl radical species within the biological medium.
