Uéslen Rocha

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 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.

Neodymium-Doped LaF (3) Nanoparticles for Fluorescence Bioimaging in the Second Biological Window

The future perspective of fluorescence imaging for real in vivo application are based on novel efficient nanoparticles which is able to emit in the second biological window (1000-1400 nm). In this work, the potential application of Nd(3+) -doped LaF(3) (Nd(3+) :LaF(3) ) nanoparticles is reported for fluorescence bioimaging in both the first and second biological windows based on their three main emission channels of Nd(3+) ions: (4) F(3/2) →(4) I(9/2) , (4) F(3/2) →(4) I(11/2) and (4) F(3/2) →(4) I(13/2) that lead to emissions at around 910, 1050, and 1330 nm, respectively. By systematically comparing the relative emission intensities, penetration depths and subtissue optical dispersion of each transition we propose that optimum subtissue images based on Nd(3+) :LaF(3) nanoparticles are obtained by using the (4) F3/2 →(4) I11/2 (1050 nm) emission band (lying in the second biological window) instead of the traditionally used (4) F(3/2) →(4) I(9/2) (910 nm, in the first biological window). After determining the optimum emission channel, it is used to obtain both in vitro and in vivo images by the controlled incorporation of Nd(3+) :LaF(3) nanoparticles in cancer cells and mice. Nd(3+) :LaF(3)nanoparticles thus emerge as very promising fluorescent nanoprobes for bioimaging in the second biological window.

1.3 μm emitting SrF2:Nd3+ nanoparticles for high contrast in vivo imaging in the second biological window

Novel approaches for high contrast, deep tissue, in vivo fluorescence biomedical imaging are based on infrared-emitting nanoparticles working in the so-called second biological window (1,000–1,400 nm). This allows for the acquisition of high resolution, deep tissue images due to the partial transparency of tissues in this particular spectral range. In addition, the optical excitation with low energy (infrared) photons also leads to a drastic reduction in the contribution of autofluorescence to the in vivo image. Nevertheless, as is demonstrated here, working solely in this biological window does not ensure a complete removal of autofluorescence as the specimen’s diet shows a remarkable infrared fluorescence that extends up to 1,100 nm. In this work, we show how the 1,340 nm emission band of Nd3+ ions embedded in SrF2 nanoparticles can be used to produce autofluorescence free, high contrast in vivo fluorescence images. It is also demonstrated that the complete removal of the food-related infrared autofluorescence is imperative for the development of reliable biodistribution studies.

Unveiling in Vivo Subcutaneous Thermal Dynamics by Infrared Luminescent Nanothermometers

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.

Nd3+ doped LaF3 nanoparticles as self-monitored photo-thermal agents

In this work, we demonstrate how LaF3 nanoparticles activated with large concentrations (up to 25%) of Nd3+ ions can simultaneously operate as biologically compatible efficient nanoheaters and fluorescent nanothermometers under single beam (808u2009nm) infrared laser excitation. Nd3+:LaF3 nanoparticles emerge as unique multifunctional agents that could constitute the first step towards the future development of advanced platforms capable of simultaneous deep tissue fluorescence bio-imaging and controlled photo-thermal therapies.

Neodymium-doped nanoparticles for infrared fluorescence bioimaging: The role of the host

The spectroscopic properties of different infrared-emitting neodymium-doped nanoparticles (LaF3:Nd3+, SrF2:Nd3+, NaGdF4: Nd3+, NaYF4: Nd3+, KYF4: Nd3+, GdVO4: Nd3+, and Nd:YAG) have been systematically analyzed. A comparison of the spectral shapes of both emission and absorption spectra is presented, from which the relevant role played by the host matrix is evidenced. The lack of a “universal” optimum system for infrared bioimaging is discussed, as the specific bioimaging application and the experimental setup for infrared imaging determine the neodymium-doped nanoparticle to be preferentially used in each case.

LaF3 core/shell nanoparticles for subcutaneous heating and thermal sensing in the second biological-window

We report on Ytterbium and Neodymium codoped LaF3 core/shell nanoparticles capable of simultaneous heating and thermal sensing under single beam infrared laser excitation. Efficient light-to-heat conversion is produced at the Neodymium highly doped shell due to non-radiative de-excitations. Thermal sensing is provided by the temperature dependent Nd3+u2009→u2009Yb3+ energy transfer processes taking place at the core/shell interface. The potential application of these core/shell multifunctional nanoparticles for controlled photothermal subcutaneous treatments is also demonstrated.

Optimum quantum dot size for highly efficient fluorescence bioimaging

Semiconductor quantum dots of few nanometers have demonstrated a great potential for bioimaging. The size determines the emitted color, but it is also expected to play an important role in the image brightness. In this work, the size dependence of the fluorescence quantum yield of the highly thermal sensitive CdTe quantum dots has been systematically investigated by thermal lens spectroscopy. It has been found that an optimum quantum yield is reached for 3.8-nm quantum dots. The presence of this optimum size has been corroborated in both one-photon excited fluorescence experiments and two-photon fluorescence microscopy of dot-incubated cancer cells. Combination of quantum yield and fluorescence decay time measurements supports that the existence of this optimum size emerges from the interplay between the frequency-dependent radiative emission rate and the size-dependent coupling strength between bulk excitons and surface trapping states.

Subtissue Imaging and Thermal Monitoring of Gold Nanorods through Joined Encapsulation with Nd-Doped Infrared-Emitting Nanoparticles.

Encapsulation of gold nanorods together with Nd-doped fluorescent nanoparticles in a biocompatible polymer creates multifunctional nanostructures, whose infrared fluorescence allows their subcutaneous localization in biological tissues while also adding the ability to measure the temperature from the emitted light in order to better monitor the light-to-heat conversion of the gold nanorods during photothermal therapy.

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.