The tremendous development of nanotechnology is bringing us closer to the dream of clinical application of nanoparticles in photothermal therapies of tumors. This requires the use of specifi c nanoparticles that must be highly biocompatible, effi cient light-to-heat converters and fl uorescent markers. Temperature reading by the heating nanoparticles during therapy appears of paramount importance to keep at a minimum the collateral damage that could arise from undesirable excessive heating. In this work, this thermally controlled therapy is possible by using Nd 3+ ion-doped LaF 3 nanocrystals. Because of the particular optical features of Nd 3+ ions at high doping concentrations, these nanoparticles are capable of in vivo photothermal heating, fl uorescent tumor localization and intratumoral thermal sensing. The successful photothermal therapy experiments here presented highlight the importance of controlling therapy parameters based on intratumoral temperature measurements instead of on the traditionally used skin temperature measurements. In fact, signifi cant differences between intratumoral and skin temperatures do exist and could lead to the appearance of excessive collateral damage. These results open a new avenue for the real application of nanoparticle-based photothermal therapy at clinical level.

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 Nd³⁺: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 Nd³⁺: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: Nd³⁺: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 Nd³⁺:LaF₃ nanoparticles. The possibility of a real single-beam-controlled subtissue hyperthermia process is, therefore, pointed out.

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.

The current status of the use of luminescent nanoparticles for thermometry in animal models is reviewed in detail. The different types of luminescent nanoparticles capable of deep tissue temperature sensing are described, paying special attention to the physical mechanisms at the root of their thermal sensing capacity. Their thermal sensitivities are listed and compared. This review describes the most relevant experiments, in which luminescence nanothermometry has been successfully applied at the small animal level, including the development of controlled thermal therapies as well as subtissue diagnosis procedures. Advantages and disadvantages of different luminescent nanothermometers are discussed.

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