Ag2 S Biocompatible Ensembles as Dual OCT Contrast Agents and NIR Ocular Imaging Probes.

Ag2 S nanoparticles (NPs) emerge as a unique system that simultaneously features in vivo near-infrared (NIR) imaging, remote heating, and low toxicity thermal sensing. In this work, their capabilities are extended into the fields of optical coherence tomography (OCT), as contrast agents, and NIR probes in both ex vivo and in vivo experiments in eyeballs. The new dual property for ocular imaging is obtained by the preparation of Ag2 S NPs ensembles with a biocompatible amphiphilic block copolymer. Rather than a classical ligand exchange, where surface traps may arise due to incomplete replacement of surface sites, the use of this polymer provides a protective extra layer that preserves the photoluminescence properties of the NPs, and the procedure allows for the controlled preparation of submicrometric scattering centers. The resulting NPs ensembles show extraordinary colloidal stability with time and biocompatibility, enhancing the contrast in OCT with simultaneous NIR imaging in the second biological window.

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.

Biological studies of an ICG-tagged aptamer as drug delivery system for malignant melanoma.

Malignant melanoma accounts for about 1% of all skin malignant tumors and represents the most aggressive and lethal form of skin cancer. Clinically, there exist different therapeutic options for melanoma treatment, such as surgery, chemotherapy, radiotherapy, photodynamic therapy and immunotherapy. However, serious adverse effects usually arise, and survival rates are still low because a high number of patients present relapses within 6-9 months after therapy. AS1411 is a G-quadruplex (G4) aptamer capable of tumor-specific recognition, since it binds to nucleolin, a multi-functional protein expressed in many different types of cancer cells. In this work, we present a novel drug delivery system composed of AS1411 and indocyanine green (ICG) to track its accumulation in tumoral cells in a melanoma mouse model. Using a simple supramolecular strategy, we conjugated the complex AS1411-ICG with C8 ligand, an acridine orange derivative with potential anticancer ligand. Then, we performed in vitro cytotoxicity experiments using the B16 mouse melanoma cell line, and in vivo experiments using a B16 mouse melanoma model to study biodistribution and histological changes. The circular dichroism (CD) data suggest that C8 does not affect the parallel G4 topology of AS1411-ICG, whereas it increases its thermal stability. Incubation of B16 melanoma cells with the AS1411-ICG complex associated with C8 increases the cytotoxicity compared with AS1411-ICG alone. From the in vivo studies, we conclude that both AS1411-ICG and AS1411-ICG-C8 presented the potential to accumulate preferentially in tumor tissues. Moreover, these compounds seem to be efficiently removed from the mice's bodies through kidney clearance. In summary, these results suggest that these complexes derived from AS1411 aptamer could act as a delivery system of ligands with antitumoral activity for in vivo melanoma therapy.

Instantaneous In Vivo Imaging of Acute Myocardial Infarct by NIR-II Luminescent Nanodots.

Fast and precise localization of ischemic tissues in the myocardium after an acute infarct is required by clinicians as the first step toward accurate and efficient treatment. Nowadays, diagnosis of a heart attack at early times is based on biochemical blood analysis (detection of cardiac enzymes) or by ultrasound-assisted imaging. Alternative approaches are investigated to overcome the limitations of these classical techniques (time-consuming procedures or low spatial resolution). As occurs in many other fields of biomedicine, cardiological preclinical imaging can also benefit from the fast development of nanotechnology. Indeed, bio-functionalized near-infrared-emitting nanoparticles are herein used for in vivo imaging of the heart after an acute myocardial infarct. Taking advantage of the superior acquisition speed of near-infrared fluorescence imaging, and of the efficient selective targeting of the near-infrared-emitting nanoparticles, in vivo images of the infarcted heart are obtained only a few minutes after the acute infarction event. This work opens an avenue toward cost-effective, fast, and accurate in vivo imaging of the ischemic myocardium after an acute infarct.

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.

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.

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.