Advancing neodymium single-band nanothermometry.

Near-infrared (NIR) emitting contrast agents with integrated optical temperature sensing are highly desirable for a variety of biomedical applications, particularly when subcutaneous target visualization and measurement of its thermodynamic properties are required. To that end, the possibility of using Nd3+ doped LiLuF4 rare-earth nanoparticles (RENPs) as NIR photoluminescent nanothermometers is explored. These RENPs are relatively small, have narrow size distribution, and can easily be core/shell engineered - all combined, these features meet the requirements of biologically relevant and multifunctional nanoprobes. The LiLuF4 host allows to observe the fine Stark structure of the 4F3/2→4I9/2, 4I11/2, and 4I13/2 optical transitions, each of which can then be used for single-band NIR nanothermometry. The thermometric parameter defined for the most intense Nd3+ emission around 1050 nm, shows high temperature sensitivity (∼0.49% °C-1), and low temperature uncertainty (0.3 °C) as compared to the thermometric parameters defined for the 880 and 1320 nm Nd3+ emissions. Additionally, transient temperature measurements through tissue show that these RENPs can be used to assess fast temperature changes at a tissue depth of 3 mm, while slower temperature changes can be measured at even greater depths. Nd3+ doped LiLuF4 RENPs represent a significant improvement for Nd3+ based single-band photoluminescence nanothermometry, with the possibility of its integration within more sophisticated multifunctional theranostic nanostructures.

Tuning the sensitivity of lanthanide-activated NIR nanothermometers in the biological windows.

Lanthanide-activated SrF2 nanoparticles with a multishell architecture were investigated as optical thermometers in the biological windows. A ratiometric approach based on the relative changes in the intensities of different lanthanide (Nd3+ and Yb3+) NIR emissions was applied to investigate the thermometric properties of the nanoparticles. It was found that an appropriate doping with Er3+ ions can increase the thermometric properties of the Nd3+-Yb3+ coupled systems. In addition, a core containing Yb3+ and Tm3+ can generate light in the visible and UV regions upon near-infrared (NIR) laser excitation at 980 nm. The multishell structure combined with the rational choice of dopants proves to be particularly important to control and enhance the performance of nanoparticles as NIR nanothermometers.

Covering the optical spectrum through collective rare-earth doping of NaGdF4 nanoparticles: 806 and 980 nm excitation routes.

Today, at the frontier of biomedical research, the need has been clearly established for integrating disease detection and therapeutic function in one single theranostic system. Light-emitting nanoparticles are being intensively investigated to fulfil this demand, by continuously developing nanoparticle systems simultaneously emitting in both the UV/visible (light-triggered release and activation of drugs) and the near-infrared (imaging and tracking) spectral regions. In this work, rare-earth (RE) doped nanoparticles (RENPs) were synthesized via a thermal decomposition process and spectroscopically investigated as potential candidates as all-in-one optical imaging, diagnostic and therapeutic agents. These core/shell/shell nanoparticles (NaGdF4:Er3+,Ho3+,Yb3+/NaGdF4:Nd3+,Yb3+/NaGdF4) are optically excited by heating-free 806 nm light that, aside from minimizing the local thermal load, also allows to obtain a deeper sub-tissue penetration with respect to the still widely used 980 nm light. Moreover, these water-dispersed nanoplatforms offer interesting assets as triggers/probes for biomedical applications, by virtue of a plethora of emission bands (spanning the 380-1600 nm range). Our results pave the way to use these RENPs for UV/visible-triggered photodynamic therapy/drug release, while simultaneously tracking the nanoparticle biodistribution and monitoring their therapeutic action through the near-infrared signal that overlaps with biological transparency windows.

Double rare-earth nanothermometer in aqueous media: opening the third optical transparency window to temperature sensing.

Owing to the alluring possibility of contactless temperature probing with microscopic spatial resolution, photoluminescence nanothermometry at the nanoscale is rapidly advancing towards its successful application in biomedical sciences. The emergence of near-infrared nanothermometers has paved the way for temperature sensing at the deep tissue level. However, water dispersibility, adequate size at the nanoscale, and the capability to efficiently operate in the second and third biological optical transparency windows are the requirements that still have to be fulfilled in a single nanoprobe. In this work, these requirements are addressed by rare-earth doped nanoparticles with core/shell-architecture, dispersed in water, whose excitation and emission wavelengths conveniently fall within the biological optical transparency windows. Under heating-free 800 nm excitation, double nanothermometry is realized either with Ho3+-Nd3+ (1.18-1.34 µm) or Er3+-Nd3+ (1.55-1.34 µm) NIR emission band ratios, both displaying equal thermal sensitivities around 1.1% °C-1. It is further demonstrated that, along with the interionic energy transfer processes, the thermometric properties of these nanoparticles are also governed by the temperature dependent energy transfer to the surrounding solvent (water) molecules. Overall, this work presents a novel water dispersible double ratiometric nanothermometer operating in the second and third biological optical transparency windows. The temperature dependent particle-solvent interaction is also presented, which is critical for e.g. future in vivo applications.

Deep tissue bio-imaging using two-photon excited CdTe fluorescent quantum dots working within the biological window.

A new approach to deep tissue imaging is presented based on 8 nm CdTe semiconductor quantum dots (QDs). The characteristic 800 nm emission was found to be efficiently excited via two-photon absorption of 900 nm photons. The fact that both excitation and emission wavelengths lie within the "biological window" allows for high resolution fluorescence imaging at depths close to 2 mm. These penetration depths have been used to obtain the first deep tissue multiphoton excited fluorescence image based on CdTe-QDs. Due to the large thermal sensitivity of CdTe-QDs, one may envisage, in the near future, their use in high resolution deep-tissue thermal imaging.

Visible upconversion emission of Pr3+ doped gadolinium gallium garnet nanocrystals.

The luminescence properties of a Pr3+-doped gadolinium gallium garnet (GGG, Gd3Ga5O12) nanocrystalline host were investigated. Dominant blue/green emission was observed emanating from the 3P0 --> 3H4 transition after excitation using a wavelength of 457.9 nm. Continuous wave excitation into the 1D2 level of the Pr3+ ion at 606.9 nm transition produced blue upconversion luminescence spectra, ascribed to emission from the 3P1 --> 3H4 and 3P0 --> 3H4 transitions. The increase in the decay times of the observed transitions following excitation with 606.9 nm is indicative of the dominance of an energy transfer upconversion (ETU) mechanism relative to excited state absorption (ESA). Furthermore, blue, green and red upconversion emission was observed from the 3P0, 3P1 and 1D2 states following excitation into the 1G4 energy level with 980 nm. No change in the decay times of the emitting states was observed following excitation with a wavelength of 980 or 457.9 nm; hence, upconversion was determined to primarily occur through ESA. The luminescence properties of the nanocrystals are compared to a single crystal of GGG:Pr3+ (bulk) with an identical Pr3+ concentration (1%).