Lanthanide doped nanoparticles for reliable and precise luminescence nanothermometry in the third biological window.

In recent years, infrared emitting luminescent nanothermometers have attracted significant attention because their potential for the development of new diagnosis and therapy procedures. Despite their promising applications, concerns have been raised about their reliability due to the spectral distortions induced by tissues that are present even in the commonly used second biological window (1000-1370 nm). In this work, we present an innovative solution to this issue by demonstrating the effectiveness of shifting the operation range of these nanothermometers to the third biological window (1550-1850 nm). Through experimental evidence using ytterbium, erbium, and thulium tri-doped CaF2 nanoparticles, we demonstrate that luminescence spectra acquired in the third biological window are minimally distorted by the presence of tissue, opening the way to reliable luminescence thermometry. In addition, advanced analysis (singular value decomposition) of emission spectra allows sub-degree thermal uncertainties to be achieved.

Optical switching a photon-avalanche-like mechanism in NdAl3(BO3)4 particles excited at 1064 nm by an auxiliary beam at 808 nm.

In recent years, an unconventional excitation of trivalent neodymium ions (N d 3+) at 1064 nm, not resonant with ground-state transitions, has been investigated with the unprecedented demonstration of a photon-avalanche-like (PA-like) mechanism, in which the temperature increase plays a fundamental role. As a proof-of-concept, N d A l 3(B O 3)4 particles were used. A consequence of the PA-like mechanism is the absorption enhancement of excitation photons providing light emission at a broad range covering the visible and near-infrared spectra. In the first study, the temperature increase was due to intrinsic nonradiative relaxations from the N d 3+ and the PA-like mechanism ensued at a given excitation power threshold (P t h ). Subsequently, an external heating source was used to trigger the PA-like mechanism while keeping the excitation power below P t h at room temperature. Here, we demonstrate the switching on of the PA-like mechanism by an auxiliary beam at 808 nm, which is in resonance with the N d 3+ ground-state transition 4 I 9/2→{4 F 5/2,2 H 9/2}. It comprises the first, to the best of our knowledge, demonstration of an optical switched PA, and the underlying physical mechanism is the additional heating of the particles due to the phonon emissions from the N d 3+ relaxation pathways when exciting at 808 nm. The present results have potential applications in controlled heating and remote temperature sensing.

Role of heat treatment on the structural and luminescence properties of Yb3+/Ln3+ (Ln = Tm, Ho and Er) co-doped LaF3 nanoparticles.

Hexagonal LaF3:Yb3+/Ln3+ and tetragonal LaOF:Yb3+/Ln3+ (Ln = Ho, Tm, Er) have been successfully prepared via a two-step reaction, which includes a facile aqueous ligand free solution method and the following heat treatment of the as-prepared LaF3 precursor. The phase formation evolution from LaF3 to LaOF with different phase structures was characterized by X-ray diffraction (XRD), scanning electron microscopy, Fourier transform infrared, and Raman spectroscopy. At an annealing temperature of 500 °C pure hexagonal LaF3:Yb3+/Ln3+ (Ln = Ho, Tm, Er) nanoparticles with an average size of 32 nm were obtained and they showed a strong visible upconversion and a modest infrared emission upon 976 nm laser excitation. Further, using an annealing temperature of 900 °C, tetragonal LaOF:Yb3+/Ln3+ (Ln = Ho, Tm, Er) nanoparticles with a size of around 44 nm were obtained (obtained from XRD) and an expressive enhancement in the emission of the VIS and near-infrared regions was observed. These results envision applications that require efficient emissions such as fluorescent and thermal images, and LaF3 nanocrystals have recently been widely explored for applications in biological systems.

Ultrafast photochemistry produces superbright short-wave infrared dots for low-dose in vivo imaging.

Optical probes operating in the second near-infrared window (NIR-II, 1,000-1,700 nm), where tissues are highly transparent, have expanded the applicability of fluorescence in the biomedical field. NIR-II fluorescence enables deep-tissue imaging with micrometric resolution in animal models, but is limited by the low brightness of NIR-II probes, which prevents imaging at low excitation intensities and fluorophore concentrations. Here, we present a new generation of probes (Ag2S superdots) derived from chemically synthesized Ag2S dots, on which a protective shell is grown by femtosecond laser irradiation. This shell reduces the structural defects, causing an 80-fold enhancement of the quantum yield. PEGylated Ag2S superdots enable deep-tissue in vivo imaging at low excitation intensities (<10 mW cm-2) and doses (<0.5 mg kg-1), emerging as unrivaled contrast agents for NIR-II preclinical bioimaging. These results establish an approach for developing superbright NIR-II contrast agents based on the synergy between chemical synthesis and ultrafast laser processing.

Synthesis and characterization of Ag2S and Ag2S/Ag2(S,Se) NIR nanocrystals.

Syntheses of metal sulfide nanocrystals (NCs) by heat-up routes in the presence of thiols yield NC arrangements difficult to further functionalize and transfer to aqueous media. By means of different NMR techniques, and exemplified by Ag2S NCs, a metal-organic polymer formed during the synthesis acting as a ligand has been identified to be responsible for such aggregation. In this work, a new synthetic hot-injection strategy is presented to synthesize Ag2S NCs which are easily ligand exchangeable in water. Furthermore, the hot-injection route allows an extra NC treatment with Se to produce Ag2S/Ag2(S,Se) NCs with improved optical properties with respect to the Ag2S cores, and better resistance to oxidation, as demonstrated by X-ray absorption experiments.

Thulium doped LaF3 for nanothermometry operating over 1000 nm.

The use and applications of infrared emitting rare-earth luminescent nanoparticles as nanothermometers have attracted a great deal of attention during the last few years. Researchers have regarded rare-earth doped luminescent nanoparticles as appealing systems due to their reliability, sensitivity and versatility for minimally invasive thermal sensing in nanomedicine. The challenge of developing nanothermometers operating over 1000 nm with outstanding brightness and enhanced sensitivity is being constantly addressed. In this sense, this work explores the potential of Tm3+ emissions at around 1.23 and 1.47 µm, under excitation at 690 nm, for ratiometric thermometry in Tm3+ doped LaF3 nanoparticles. The temperature dependence of the 1.23 µm emission band, which cannot be observed in systems such as NaNbO3:Tm, was demonstrated to be very effective and presented a relative thermal sensitivity as high as 1.9% °C-1. The physical mechanisms behind the strong thermal dependences were explained in terms of multiphonon decays and cross-relaxations. As a proof of concept, the nanothermometers presented were capable of accessing the basic properties of tissues in an ex vivo experiment using thermal relaxation dynamics.

Core-shell rare-earth-doped nanostructures in biomedicine.

The current status of the use of core-shell rare-earth-doped nanoparticles in biomedical applications is reviewed in detail. The different core-shell rare-earth-doped nanoparticles developed so far are described and the most relevant examples of their application in imaging, sensing, and therapy are summarized. In addition, the advantages and disadvantages they present are discussed. Finally, a critical opinion of their potential application in real life biomedicine is given.

Lifetime-Encoded Infrared-Emitting Nanoparticles for in Vivo Multiplexed Imaging.

Advanced diagnostic procedures are required to satisfy the continuously increasing demands of modern biomedicine while also addressing the need for cost reduction in public health systems. The development of infrared luminescence-based techniques for in vivo imaging as reliable alternatives to traditional imaging enables applications with simpler and more cost-effective apparatus. To further improve the information provided by in vivo luminescence images, the design and fabrication of enhanced infrared-luminescent contrast agents is required. In this work, we demonstrate how simple dopant engineering can lead to infrared-emitting rare-earth-doped nanoparticles with tunable (0.1-1.5 ms) and medium-independent luminescence lifetimes. The combination of these tunable nanostructures with time-gated infrared imaging and time domain analysis is employed to obtain multiplexed in vivo images that are used for complex biodistribution studies.

In Vivo Ischemia Detection by Luminescent Nanothermometers.

There is an urgent need to develop new diagnosis tools for real in vivo detection of first stages of ischemia for the early treatment of cardiovascular diseases and accidents. However, traditional approaches show low sensitivity and a limited penetration into tissues, so they are only applicable for the detection of surface lesions. Here, it is shown how the superior thermal sensing capabilities of near infrared-emitting quantum dots (NIR-QDs) can be efficiently used for in vivo detection of subcutaneous ischemic tissues. In particular, NIR-QDs make possible ischemia detection by high penetration transient thermometry studies in a murine ischemic hindlimb model. NIR-QDs nanothermometers are able to identify ischemic tissues by means of their faster thermal dynamics. In addition, they have shown to be capable of monitoring both the revascularization and damage recovery processes of ischemic tissues. This work demonstrates the applicability of fluorescence nanothermometry for ischemia detection and treatment, as well as a tool for early diagnosis of cardiovascular disease.

Correction: Self-monitored photothermal nanoparticles based on core-shell engineering.

Correction for 'Self-monitored photothermal nanoparticles based on core-shell engineering' by Erving C. Ximendes et al., Nanoscale, 2016, 8, 3057-3066.

Unveiling in Vivo Subcutaneous Thermal Dynamics by Infrared Luminescent Nanothermometers.

The recent development of core/shell engineering of rare earth doped luminescent nanoparticles has ushered a new era in fluorescence thermal biosensing, allowing for the performance of minimally invasive experiments, not only in living cells but also in more challenging small animal models. Here, the potential use of active-core/active-shell Nd(3+)- and Yb(3+)-doped nanoparticles as subcutaneous thermal probes has been evaluated. These temperature nanoprobes operate in the infrared transparency window of biological tissues, enabling deep temperature sensing into animal bodies thanks to the temperature dependence of their emission spectra that leads to a ratiometric temperature readout. The ability of active-core/active-shell Nd(3+)- and Yb(3+)-doped nanoparticles for unveiling fundamental tissue properties in in vivo conditions was demonstrated by subcutaneous thermal relaxation monitoring through the injected core/shell nanoparticles. The reported results evidence the potential of infrared luminescence nanothermometry as a diagnosis tool at the small animal level.

Self-monitored photothermal nanoparticles based on core-shell engineering.

The continuous development of nanotechnology has resulted in the actual possibility of the design and synthesis of nanostructured materials with pre-tailored functionabilities. Nanostructures capable of simultaneous heating and local thermal sensing are in strong demand as they would constitute a revolutionary solution to several challenging problems in bio-medicine, including the achievement of real time control during photothermal therapies. Several approaches have been demonstrated to achieve simultaneous heating and thermal sensing at the nanoscale. Some of them lack of sufficient thermal sensitivity and others require complicated synthesis procedures for heterostructure fabrication. In this study, we demonstrate how single core/shell dielectric nanoparticles with a highly Nd(3+) ion doped shell and an Yb(3+),Er(3+) codoped core are capable of simultaneous thermal sensing and heating under an 808 nm single beam excitation. The spatial separation between the heating shell and sensing core provides remarkable values of the heating efficiency and thermal sensitivity, enabling their application in single beam-controlled heating experiments in both aqueous and tissue environments.

Neodymium-doped LaF(3) nanoparticles for fluorescence bioimaging in the second biological window.

The future perspective of fluorescence imaging for real in vivo application are based on novel efficient nanoparticles which is able to emit in the second biological window (1000-1400 nm). In this work, the potential application of Nd(3+) -doped LaF(3) (Nd(3+) :LaF(3) ) nanoparticles is reported for fluorescence bioimaging in both the first and second biological windows based on their three main emission channels of Nd(3+) ions: (4) F(3/2) →(4) I(9/2) , (4) F(3/2) →(4) I(11/2) and (4) F(3/2) →(4) I(13/2) that lead to emissions at around 910, 1050, and 1330 nm, respectively. By systematically comparing the relative emission intensities, penetration depths and subtissue optical dispersion of each transition we propose that optimum subtissue images based on Nd(3+) :LaF(3) nanoparticles are obtained by using the (4) F3/2 →(4) I11/2 (1050 nm) emission band (lying in the second biological window) instead of the traditionally used (4) F(3/2) →(4) I(9/2) (910 nm, in the first biological window). After determining the optimum emission channel, it is used to obtain both in vitro and in vivo images by the controlled incorporation of Nd(3+) :LaF(3) nanoparticles in cancer cells and mice. Nd(3+) :LaF(3)nanoparticles thus emerge as very promising fluorescent nanoprobes for bioimaging in the second biological window.

Two photon thermal sensing in Er3+/Yb3+ co-doped nanocrystalline NaNbO3.

We investigate the potential use of two-photon absorption of Er3+/Yb3+ co-doped NaNbO3 nanocrystals for nanothermometry as well as thermal imaging, based on the thermally coupled green Er3+ emission lines. In fact, thermal sensor in the range of 20-80 degrees C with -0.1 degrees C accuracy using excitation powers readily obtained from commercially available semiconductor laser was achieved. The pump-intensity induced local heating was also investigated upon femtosecond laser excitation and 0.55 K/kW x cm(-2) was achieved. The highly efficient green emission together with two-photon dependence and femtosecond laser excitation should increase the brightness of thermal imaging. Additionally, the high temperature-sensitive fluorescence, when compared to previous literatures, should increase the resolution of nanothermometers.

Ultrasensitive thermal lens spectroscopy of water.

A recently developed dual-beam configuration that optimizes the thermal lens technique has been used to obtain the absorption spectrum of pure water from 350 to 528 nm. Our results indicate the minimum linear absorption coefficient smaller than 2 x 10(-5) cm(-1) between 360 and 400 nm. This value is lower than previous literature data, and it is blueshifted. Absorption coefficients as small as 2 x 10(-7) cm(-1) can be measured for water using 1 W of excitation power. A detection limit of approximately 6 x 10(-9) cm(-1)(P=1 W) for CCl(4) was estimated, which represents, to the best of our knowledge, the highest sensitivity obtained in small absorption measurements in liquids.

Upconversion effect on fluorescence quantum efficiency and heat generation in Nd3+-doped materials.

The thermal lens technique was carried out to experimentally determine the influence of the energy transfer upconversion (ETU) processes on fluorescence quantum efficiency (eta) in Nd3+-doped materials. The samples with high Nd3+ concentration present a considerable reduction in eta?with the increasing excitation power due to the efficient ETU processes. Besides, the energy migration was identified as the mechanism responsible for the upconversion losses. In addition, it was verified that the critical inversion density is not concentration independent, as previously stated, but it decreases with the Nd concentration. Our results point out the approach based on TL technique as a valuable alternative because of its sensitivity allowing the measurements to be performed in a pump power regime that avoids damages in the investigated material.

Conducta fotomaniaca y esquizofrenia / Photomaniac behavior, and schizophrenia

En dos pacientes con esquizofrenia residual de curso crónico según DSM-III-R se observó una marcada tolerancia a la luz intensa, manifiesta por la falta de encandilamiento y de dlolor al mirar al Sol en forma directa. La luz suprime la secreción melatonínica, reflejándose en el ritmo de esta última la exposición/ oscuridad del sujeto. La conducta de carácter fotomaníaco (o fenómenos favorecedores de la misma) recuerda a su "opuesto", la conducta fotofóbica (descrita en casos de depresión) y puede condiconar un perfil de exposición lumínica diferente. El conocimiento de estos fenómenos, que carecen actualmente de explicación, puede ser de utilidad metodológica ( o de carácter heurístico) en el estudio de procesos neuroendocrinos fotosensibles en pacietnes psiquiatricos que los presenten

Conducta fotomaniaca y esquizofrenia / Photomaniac behavior, and schizophrenia

En dos pacientes con esquizofrenia residual de curso crónico según DSM-III-R se observó una marcada tolerancia a la luz intensa, manifiesta por la falta de encandilamiento y de dlolor al mirar al Sol en forma directa. La luz suprime la secreción melatonínica, reflejándose en el ritmo de esta última la exposición/ oscuridad del sujeto. La conducta de carácter fotomaníaco (o fenómenos favorecedores de la misma) recuerda a su "opuesto", la conducta fotofóbica (descrita en casos de depresión) y puede condiconar un perfil de exposición lumínica diferente. El conocimiento de estos fenómenos, que carecen actualmente de explicación, puede ser de utilidad metodológica ( o de carácter heurístico) en el estudio de procesos neuroendocrinos fotosensibles en pacietnes psiquiatricos que los presenten (AU)