Optical detection of atherosclerosis at molecular level by optical coherence tomography: An in vitro study.

There is an urgent need for contrast agents to detect the first inflammation stage of atherosclerosis by cardiovascular optical coherence tomography (CV-OCT), the imaging technique with the highest spatial resolution and sensitivity of those used during coronary interventions. Gold nanoshells (GNSs) provide the strongest signal by CV-OCT. GNSs are functionalized with the cLABL peptide that binds specifically to the ICAM-1 molecule upregulated in the first stage of atherosclerosis. Dark field microscopy and CV-OCT are used to evaluate the specific adhesion of these functionalized GNSs to activated endothelial cells. This adhesion is investigated under static and dynamic conditions, for shear stresses comparable to those of physiological conditions. An increase in the scattering signal given by the functionalized GNSs attached to activated cells is observed compared to non-activated cells. Thus, cLABL-functionalized GNSs behave as excellent contrast agents for CV-OCT and promise a novel strategy for clinical molecular imaging of atherosclerosis.

Optical Forces at the Nanoscale: Size and Electrostatic Effects.

The reduced magnitude of the optical trapping forces exerted over sub-200 nm dielectric nanoparticles complicates their optical manipulation, hindering the development of techniques and studies based on it. Improvement of trapping capabilities for such tiny objects requires a deep understanding of the mechanisms beneath them. Traditionally, the optical forces acting on dielectric nanoparticles have been only correlated with their volume, and the size has been traditionally identified as a key parameter. However, the most recently published research results have shown that the electrostatic characteristics of a sub-100 nm dielectric particle could also play a significant role. Indeed, at present it is not clear what optical forces depend. In this work, we designed a set of experiments in order to elucidate the different mechanism and properties (i.e., size and/or electrostatic properties) that governs the magnitude of optical forces. The comparison between experimental data and numerical simulations have shown that the double layer induced at nanoparticle's surface, not considered in the classical description of nanoparticle's polarizability, plays a relevant role determining the magnitude of the optical forces. Here, the presented results constitute the first step toward the development of the dielectric nanoparticle over which enhanced optical forces could be exerted, enabling their optical manipulation for multiples purposes ranging from fundamental to applied studies.

Unveiling Molecular Changes in Water by Small Luminescent Nanoparticles.

Nowadays a large variety of applications are based on solid nanoparticles dispersed in liquids-so called nanofluids. The interaction between the fluid and the nanoparticles plays a decisive role in the physical properties of the nanofluid. A novel approach based on the nonradiative energy transfer between two small luminescent nanocrystals (GdVO4 :Nd3+ and GdVO4 :Yb3+ ) dispersed in water is used in this work to investigate how temperature affects both the processes of interaction between nanoparticles and the effect of the fluid on the nanoparticles. From a systematic analysis of the effect of temperature on the GdVO4 :Nd3+ → GdVO4 :Yb3+ interparticle energy transfer, it can be concluded that a dramatic increase in the energy transfer efficiency occurs for temperatures above 45 °C. This change is properly explained by taking into account a crossover existing in diverse water properties that occurs at about this temperature. The obtained results allow elucidation on the molecular arrangement of water molecules below and above this crossover temperature. In addition, it is observed that an energy transfer process is produced as a result of interparticle collisions that induce irreversible ion exchange between the interacting nanoparticles.

Quantum dot thermometry evaluation of geometry dependent heating efficiency in gold nanoparticles.

Quantum dot based thermometry, in combination with double beam confocal microscopy, was used to investigate the absorption/heating efficiency of gold nanoparticles with different morphologies (nanorods, nanocages, nanoshells, and nanostars), all of them with an intense localized surface plasmon resonance within the first biological window, at around 808 nm. The heating efficiency was found to be strongly dependent on the geometry of the nanostructure, with the largest values found for gold nanorods and long-edge gold nanostars, both of them with heating efficiencies close to 100%. Gold nanorods and nanocages were found to have the largest absorption cross section per unit mass among all the studied geometries, emerging as optimum photothermal agents with minimum metal loading for biosystems.

Bismuth Selenide Nanostructured Clusters as Optical Coherence Tomography Contrast Agents: Beyond Gold-Based Particles.

Optical coherence tomography (OCT) is an imaging technique currently used in clinical practice to obtain optical biopsies of different biological tissues in a minimally invasive way. Among the contrast agents proposed to increase the efficacy of this imaging method, gold nanoshells (GNSs) are the best performing ones. However, their preparation is generally time-consuming, and they are intrinsically costly to produce. Herein, we propose a more affordable alternative to these contrast agents: Bi2Se3 nanostructured clusters with a desert rose-like morphology prepared via a microwave-assisted method. The structures are prepared in a matter of minutes, feature strong near-infrared extinction properties, and are biocompatible. They also boast a photon-to-heat conversion efficiency of close to 50%, making them good candidates as photothermal therapy agents. In vitro studies evidence the prowess of Bi2Se3 clusters as OCT contrast agents and prove that their performance is comparable to that of GNSs.

Molecular Imaging of Infarcted Heart by Biofunctionalized Gold Nanoshells.

The unique combination of physical and optical properties of silica (core)/gold (shell) nanoparticles (gold nanoshells) makes them especially suitable for biomedicine. Gold nanoshells are used from high-resolution in vivo imaging to in vivo photothermal tumor treatment. Furthermore, their large scattering cross-section in the second biological window (1000-1700 nm) makes them also especially adequate for molecular optical coherence tomography (OCT). In this work, it is demonstrated that, after suitable functionalization, gold nanoshells in combination with clinical OCT systems are capable of imaging damage in the myocardium following an infarct. Since both inflammation and apoptosis are two of the main mechanisms underlying myocardial damage after ischemia, such damage imaging is achieved by endowing gold nanoshells with selective affinity for the inflammatory marker intercellular adhesion molecule 1 (ICAM-1), and the apoptotic marker phosphatidylserine. The results here presented constitute a first step toward a fast, safe, and accurate diagnosis of damaged tissue within infarcted hearts at the molecular level by means of the highly sensitive OCT interferometric technique.

Reliability of rare-earth-doped infrared luminescent nanothermometers.

The use of infrared-emitting rare-earth-doped luminescent nanoparticles as nanothermometers has attracted great attention during the last few years. The scientific community has identified rare-earth-doped luminescent nanoparticles as one of the most sensitive and versatile systems for contactless local temperature sensing in a great variety of fields, but especially in nanomedicine. Researchers are nowadays focused on the design and development of multifunctional nanothermometers with new spectral operation ranges, outstanding brightness, and enhanced sensitivities. However, no attention has been paid to the assessment of the actual reliability of the measurements provided by rare-earth-doped luminescent nanothermometers. In fact, it is assumed that they are ideal temperature sensors. Nevertheless, this is far from being true. In this work we demonstrate that the emission spectra of rare-earth-doped nanothermometers can be affected by numerous environmental and experimental factors. These include the numerical aperture of the optical elements used for their optical excitation and luminescence collection, the local concentration of nanothermometers, optical length variations, self-absorption of the luminescence by the nanothermometers themselves, and solvent optical absorption. This work concludes that rare-earth-doped luminescent nanothermometers are not as reliable as thought and, consequently, special care has to be taken when extracting temperature estimations from the variation of their emission spectra.

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.

Dynamic single gold nanoparticle visualization by clinical intracoronary optical coherence tomography.

The potential use of Gold Nanoparticles (GNPs) as contrast agents for clinical intracoronary frequency domain Optical Coherence Tomography (OCT) is here explored. The OCT contrast enhancement caused by GNPs of different sizes and morphologies has been systematically investigated and correlated with their optical properties. Among the different GNPs commercially available with plasmon resonances close to the operating wavelength of intracoronary OCT (1.3 µm), Gold Nanoshells (GNSs) have provided the best OCT contrast due to their largest scattering cross section at this wavelength. Clinical intracoronary OCT catheters are here demonstrated to be capable of three dimensional visualization and real-time tracking of individual GNSs. Results here included open an avenue to novel application of intravascular clinical OCT in combination with GNPs, such as real time evaluation of intravascular obstructions or pressure gradients.

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.

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.

Subtissue thermal sensing based on neodymium-doped LaF3 nanoparticles.

In this work, we report the multifunctional character of neodymium-doped LaF3 core/shell nanoparticles. Because of the spectral overlap of the neodymium emission bands with the transparency windows of human tissues, these nanoparticles emerge as relevant subtissue optical probes. For neodymium contents optimizing the luminescence brightness of Nd³âº:LaF3 nanoparticles, subtissue penetration depths of several millimeters have been demonstrated. At the same time, it has been found that the infrared emission bands of Nd³âº:LaF3 nanoparticles show a remarkable thermal sensitivity, so that they can be advantageously used as luminescent nanothermometers for subtissue thermal sensing. This possibility has been demonstrated in this work: Nd³âº:LaF3 nanoparticles have been used to provide optical control over subtissue temperature in a single-beam plasmonic-mediated heating experiment. In this experiment, gold nanorods are used as nanoheaters while thermal reading is performed by the Nd³âº:LaF3 nanoparticles. The possibility of a real single-beam-controlled subtissue hyperthermia process is, therefore, pointed out.

Temperature sensing using fluorescent nanothermometers.

Acquiring the temperature of a single living cell is not a trivial task. In this paper, we devise a novel nanothermometer, capable of accurately determining the temperature of solutions as well as biological systems such as HeLa cancer cells. The nanothermometer is based on the temperature-sensitive fluorescence of NaYF(4):Er(3+),Yb(3+) nanoparticles, where the intensity ratio of the green fluorescence bands of the Er(3+) dopant ions ((2)H(11/2) --> (4)I(15/2) and (4)S(3/2) --> (4)I(15/2)) changes with temperature. The nanothermometers were first used to obtain thermal profiles created when heating a colloidal solution of NaYF(4):Er(3+),Yb(3+) nanoparticles in water using a pump-probe experiment. Following incubation of the nanoparticles with HeLa cervical cancer cells and their subsequent uptake, the fluorescent nanothermometers measured the internal temperature of the living cell from 25 degrees C to its thermally induced death at 45 degrees C.