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.
The always present and undesired contribution of autofluorescence is here completely avoided by combining a simple time gating technology with long lifetime neodymium doped infrared‐emitting ...nanoparticles.
Hybrid nanostructures containing neodymium‐doped nanoparticles and infrared‐emitting quantum dots constitute highly sensitive luminescent thermometers operating in the second biological window. They ...demonstrate that accurate subtissue fluorescence thermal sensing is possible.
Magnetic nanoparticles (M:NPs) are unique agents for in vivo thermal therapies due to their multimodal capacity for efficient heat generation under optical and/or magnetic excitation. Nevertheless, ...their transfer from laboratory to the clinic is hampered by the absence of thermal feedback and by the influence that external conditions (e.g., agglomeration and biological matrix interactions) have on their heating efficiency. Overcoming these limitations requires, first, the implementation of strategies providing thermal sensing to M:NPs in order to obtain in situ thermal feedback during thermal therapies. At the same time, M:NPs should be modified so that their heating efficiency will be maintained independently of the environment and the added capability for thermometry. In this work, optomagnetic hybrid nanostructures (OMHSs) that simultaneously satisfy these two conditions are presented. Polymeric encapsulation of M:NPs with neodymium‐doped nanoparticles results in a hybrid structure capable of subtissue thermal feedback while making the heating efficiency of M:NPs independent of the medium. The potential application of the OMHSs herein developed for fully controlled thermal therapies is demonstrated by an ex vivo endoscope‐assisted controlled intracoronary heating experiment.
The combination of magnetic nanoparticles and luminescent nanothermometers through encapsulation with a polymer into optomagnetic hybrid nanostructures achieves in situ control of thermal therapies inside biological tissues. The magnetic and luminescent properties of the constituting nanoparticles are maintained, and the robustness of the thermal feedback during photothermal and/or magnetic heating is demonstrated.
Biomedicine is continuously demanding new luminescent materials to be used as optical probes for the acquisition of high resolution, high contrast and high penetration in vivo images. These ...materials, in combination with advanced techniques, could constitute the first step towards new diagnosis and therapy tools. In this work, we report on the synthesis of long lifetime rare-earth-doped fluoride nanoparticles by adopting different strategies: core/shell and dopant engineering. The here developed nanoparticles show intense infrared emission in the second biological window with a long luminescence lifetime close to 1 millisecond. These two properties make the here presented nanoparticles excellent candidates for time-gated infrared optical bioimaging. Indeed, their potential application as optical imaging contrast agents for autofluorescence-free in vivo small animal imaging has been demonstrated, allowing high contrast real-time tracking of gastrointestinal absorption of nanoparticles and transcranial imaging of intracerebrally injected nanoparticles in the murine brain.
The development of selective and controlled photo-thermal therapies requires luminescent nanoparticles capable of simultaneous heating and contactless thermal sensing. Until now, thermal therapies ...have suffered from a lack of control over the absolute temperature of the treated tissue because the nanothermometers used for thermal feedback, based on a spectral analysis of emitted radiation, were affected by the inhomogeneous extinction of the tissues. This work shows how this deficiency can be overcome by using core-shell-shell nanostructures doped with lanthanide ions (Nd3+ and Yb3+). Thermal reading was achieved from the analysis of the Yb3+ luminescence lifetime whereas simultaneous heating was achieved thanks to the non-radiative deexcitations of Nd3+ ions. Simple proof-of-concept experiments show the great potential of these lanthanide-doped nanostructures for the development of in vivo photo-thermal treatments with absolute and reliable thermal feedback.
•We have demonstrated lanthanide-doped core-shell-shell nanoparticles capable of simultaneous heating and thermal sensing under infrared laser excitation.•The fluorescence decay time provides a thermal indicator that is not affected by tissue-induced distortions.•The results demonstrate a new path towards in vivo photothermal therapy with real time, fine and absolute thermal control.
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.
Neodymium-doped yttrium aluminum garnet (YAG:Nd
) has been widely developed during roughly the past 60 years and has been an outstanding fluorescent material. It has been considered as the gold ...standard among multipurpose solid-state lasers. Yet, the successful downsizing of this system into the nanoregimen has been elusive, so far. Indeed, the synthesis of a garnet structure at the nanoscale, with enough crystalline quality for optical applications, was found to be quite challenging. Here, we present an improved solvothermal synthesis method producing YAG:Nd
nanocrystals of remarkably good structural quality. Adequate surface functionalization using asymmetric double-hydrophilic block copolymers, constituted of a metal-binding block and a neutral water-soluble block, provides stabilized YAG:Nd
nanocrystals with long-term colloidal stability in aqueous suspensions. These newly stabilized nanoprobes offer spectroscopic quality (long lifetimes, narrow emission lines, and large Stokes shifts) close to that of bulk YAG:Nd
. The narrow emission lines of YAG:Nd
nanocrystals are exploited by differential infrared fluorescence imaging, thus achieving an autofluorescence-free
readout. In addition, nanothermometry measurements, based on the ratiometric fluorescence of the stabilized YAG:Nd
nanocrystals, are demonstrated. The progress here reported paves the way for the implementation of this new stabilized YAG:Nd
system in the preclinical arena.
Functionalized upconverting nanoparticles (UCNPs) are promising theragnostic nanomaterials for simultaneous therapeutic and diagnostic purposes. We present two types of non-toxic eosin Y (EY) ...nanoconjugates derived from UCNPs as novel nanophotosensitizers (nano-PS) and deep-tissue bioimaging agents employing light at 800 nm. This excitation wavelength ensures minimum cell damage, since the absorption of water is negligible, and increases tissue penetration, enhancing the specificity of the photodynamic treatment (PDT). These UCNPs are uniquely qualified to fulfil three important roles: as nanocarriers, as energy-transfer materials, and as contrast agents. First, the UCNPs enable the transport of EY across the cell membrane of living HeLa cells that would not be possible otherwise. This cellular internalization facilitates the use of such EY-functionalized UCNPs as nano-PS and allows the generation of reactive oxygen species (ROS) under 800 nm light inside the cell. This becomes possible due to the upconversion and energy transfer processes within the UCNPs, circumventing the excitation of EY by green light, which is incompatible with deep tissue applications. Moreover, the functionalized UCNPs present deep tissue NIR-II fluorescence under 808 nm excitation, thus demonstrating their potential as bioimaging agents in the NIR-II biological window.
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