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

P. Cortelletti ^a, A. Skripka ^b, C. Facciotti‡ ^a, M. Pedroni ^a, G. Caputo ^c, N. Pinna ^d, M. Quintanilla§ ^b, A. Benayas¶ ^b, F. Vetrone *^bef and A. Speghini *^a
aNanomaterials Research Group, Dipartimento di Biotecnologie, Università di Verona and INSTM, UdR Verona, Strada Le Grazie 15, I-37134 Verona, Italy. E-mail: adolfo.speghini@univr.it
^bCentre Énergie, Matériaux et Télécommunications, Institut National de la Recherche Scientifique, Université du Québec, Varennes, QC J3X 1S2, Canada. E-mail: vetrone@emt.inrs.ca
^cSmart Materials, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy
^dInstitut für Chemie, Humboldt Universität zu Berlin, Brook-Taylor-Straße 2, 12489 Berlin, Germany
^eCentre for Self-Assembled Chemical Structures, McGill University, Montréal, Québec H3A 2K6, Canada
^fInstitute of Fundamental and Frontier Science, University of Electronic Science and Technology of China, Chengdu 610051, China

First published on 29th December 2017

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Introduction

Luminescent nanoprobes in the optical range (ultraviolet (UV), visible and near-infrared (NIR) regions) are becoming very important in biomedicine, particularly as materials for diagnostics and imaging.¹ In recent years, much effort has been devoted to engineering various functional nanomaterials with unique features, and ultimately integrate them in unique nanostructures with enhanced multimodal capabilities.^2,3 Lanthanide (Ln)-doped upconverting nanoparticles (UCNPs) are excellent optical nanoprobes⁴ and have been studied for use in in vivo optical imaging due to their emissions in the so-called biological optical transparency windows. In fact, NIR optical radiation penetrates deeper into biological tissues because it is less absorbed and scattered than visible light by the biological tissue constituents.^5–7 Many Ln-doped UCNPs can harvest light at a wavelength of 980 nm by means of the Yb³⁺ ion acting as a sensitizer.⁸ Excitation at this wavelength to generate upconversion (UC) emission can result in significant absorption of 980 nm light by water and undesirable local heating, which may be detrimental for in vivo applications. Recently, to overcome these drawbacks, the Nd³⁺ ion has been investigated as a possible sensitizer for UC, since Nd³⁺ activated nanoparticles (NPs) can convert NIR radiation around 800 nm in the first biological optical window (I-BW, 750–950 nm range) to visible light (UC emission) as well as to Stokes NIR emission in the second biological optical window (II-BW, 1000–1400 nm range).^9,10 More importantly, water absorption of 800 nm radiation is lower compared to that of 980 nm excitation, which greatly minimizes optical heating.¹¹

Ln-doped UCNPs can also be designed with core@shell (C@S) architectures, which typically increase their overall emission intensity and allow them to achieve specific energy transfer (ET) processes among the Ln ions.^12–14 The emission enhancement is achieved by reducing the surface based non-radiative processes such as multiphonon relaxation due to the interaction of the solvent molecules (water, in the case of biomedical applications) with the superficial Ln ions. Furthermore, the C@S structure allows for the promotion and/or reduction of specific ET processes among Ln ions by choosing a proper shell composition.^15–17 Thus, the appropriate design of C@S NPs yields desired luminescence features,¹⁷ not only for imaging but also to trigger other light activated systems such as photosensitizers for photodynamic therapy applications.^18–20

In modern medicine, real-time temperature sensing is of paramount importance as a diagnostic tool for diseases that induce a local temperature rise in biological tissues, or for temperature monitoring during photothermal tumor treatment to prevent excessive heating and therefore healthy tissue damage. Consequently, a desirable feature for multifunctional luminescent nanoprobes is the capability to measure temperature by monitoring optical spectral changes.^21,22 These systems play an important role in nanomedicine,^23–25 since their nanosized nature permits the evaluation of local temperature with high spatial resolution within a single cell or even at the subcellular level.^26,27 Ln-based nanostructured materials are particularly effective as thermal probes due to the unique arrangement of their energy levels, which results in multiple temperature sensitive luminescence bands.²⁸ Many luminescent nanothermometers (NTs) are based on ratiometric temperature sensing, which involves taking the ratio between the integrated signals of two well-defined emission bands.^29–32 Recently, some interesting studies have described the utility of the Nd³⁺ ion as a dopant in some fluoride hosts,^33–36 not only for radiation harvesting but also for luminescence nanothermometry. In particular, Nd³⁺ doped LaF₃,^5,37,38 NaGdF₄³⁹ and NaYF₄⁴⁰ NPs (as well as C@S NPs),^41,42 have been investigated as NIR temperature sensors using 800 nm as the excitation wavelength (in the I-BW) and collecting NIR emission in different BWs. Although most studies have focused on the aforementioned hosts, alkaline-earth based fluorides (such as CaF₂ and SrF₂) have been recently demonstrated to be very versatile and efficient hosts for Ln doping, which is also due to their low phonon energies.^43,44 In particular, SrF₂ based NPs show strong UC properties and temperature sensitive emissions in the UV, visible, and NIR regions, as well as strong luminescence in the NIR region for bioimaging.^45–49 These fluoride hosts are also easily prepared via facile, “green chemistry”, environmentally friendly methods, using water as the solvent and low temperature (<200 °C) conditions.

The aim of the present investigation is to develop Ln-doped multishell SrF₂ NPs as visible-NIR optical probes and NTs. By choosing Nd³⁺, Yb³⁺, Er³⁺ and Tm³⁺ as dopant ions, the present multishell NPs (MNPs) are rationally designed to harvest 806 nm or 980 nm radiation to emit UC and Stokes radiation. Furthermore the influence of Er³⁺ ions on the thermometric properties is also investigated.

Experimental

Preparation of multishell NPs

Multishell NPs were synthesized in four sequential hydrothermal reaction steps.^45,50 In each synthetic step, metal chloride powder in the proper stoichiometric ratios was dissolved in 20 mL of deionized water (final metal concentration 0.2 M) and potassium citrate added as the capping agent (1 M, final concentration). The solution was stirred until all the reagents dissolved and an aqueous solution of NH₄F was added to give a F:(Ln³⁺ + Sr²⁺) ratio of 2.5. All reagents (99.9% purity) were purchased from Sigma-Aldrich and used without further purification. The resulting solution was sealed in a steel autoclave and heated at 190 °C for 3 h.⁴⁷ The NPs were then precipitated with acetone or ethanol and collected by centrifugation. The resulting gel was stored under acetone without any degradation. Also, the NPs formed very transparent colloidal suspensions when dissolved in water. For each shell the reaction was repeated using the same experimental conditions except for the Ln ion concentration. The dopant concentrations for the MNPs were:

SrF₂:Yb(22%),Tm(0.2%)@Y(22%)@Yb(19%),Er(x%),Nd(1%)@Nd(22%), with x = 0, 0.2, 1.0, 2.0, 4.0 and 8.0.

The Ln concentration refers to the total metal content (in mol) in the core or shell layers (see Scheme 1).

The 1^st shell was singly doped with spectroscopically silent Y³⁺ ions to minimize ET processes among the Ln ions in the core and the 2^nd shell. The 3^rd shell contained only Nd³⁺ ions at a high concentration (22%) for efficient harvesting of radiation at 800 nm. Additionally, the Er³⁺ ion concentration in the 2^nd shell was varied to investigate the influence of Er³⁺ ions on the NIR emissions of the Nd³⁺ and Yb³⁺ ions in the different MNPs.

Structural analysis

X-ray powder diffraction (XRPD) patterns were measured using a Thermo ARL X'TRA powder diffractometer equipped with a Cu based X-ray source. The cell parameters for the cubic structures were determined from the XRPD reflections. The crystallite size for the multishell structures was also estimated from the XRPD reflections using the Debye–Scherrer formula.

Morphology

Transmission electron microscopy (TEM) images were obtained with a CM200 LaB₆ Philips microscope operating at 200 kV. A few drops of NP dispersion was deposited on a copper grid and dried in air. The Pebbles software was used to analyze the NP size distribution.⁵¹

DLS analysis

Dynamic light scattering (DLS) measurements were carried out using a Malvern Zetasizer Nano ZS90 operating with a He–Ne laser at 633 nm. Samples were prepared as water colloidal dispersions with a 10 mg mL⁻¹ concentration using plastic disposable cuvettes. The Malvern Zetasizer software was used to obtain the hydrodynamic radius of the MNPs.

Luminescence spectroscopy and thermometric measurements

Emission spectra were measured using a Shamrock 500i monochromator (Andor) equipped with an iDus CCD detector (Andor) in the visible range or the same monochromator equipped with an iDus InGaAs (Andor) for the NIR range. CW laser diodes at 980 nm (laser power density of 27 W cm⁻²) and 806 nm (laser power density of 31 W cm⁻²) were used as the excitation sources. A temperature control stage (Quantum Northwest qpod2e) with a stirrer and a stabilization time of 10 minutes were used for temperature measurements (uncertainty of 0.02 °C). All spectroscopic measurements were performed on water colloidal dispersions of the MNPs at a concentration of 1 wt%. The uncertainties for the FIR values and consequently for relative sensitivity and minimum measurable temperature variation were evaluated considering the uncertainties of the integrated areas of the emission bands. Error propagation was used to evaluate the error bars for the corresponding thermometric quantities, as shown in the figures in the NIR thermometry section.

Results and discussion

Structural and morphological analysis

XRPD patterns for the MNPs were measured after each reaction step to check the growth of the core and each subsequent shell. The XRPD patterns for the MNP with 2% Er³⁺ are shown in Fig. S11 (ESI†) as a representative example.

All NPs present a cubic single phase (space group n. 225, Fmm) with a cell parameter of 5.74 ± 0.01 Å. As noted in Fig. SI1† for the MNPs with 2% Er³⁺ concentration in the second shell, the XRPD reflections become sharper after the growth of each shell, which also indicates a continuous increase in the MNPs size. This was confirmed by the MNP size, calculated from the XRPD pattern using the Scherrer equation and shown in Table SI1 (ESI†). The TEM images of the samples after each synthetic step confirm the epitaxial growth of multiple shells, and evidence very good size monodispersity (see Fig. 1). The hydrodynamic radius measured by the DLS technique increased after each synthetic step, as shown in Fig. SI2,† again confirming the NP growth.

UC emission

UC spectra for the MNPs water colloids upon 980 nm excitation were acquired at each reaction step, which are shown in Fig. SI3–SI5 (see ESI†), where features due to the subsequent shell formations are evident. The UC spectrum for the complete MNPs with 1% Er³⁺ upon 980 nm laser excitation is shown in Fig. 2, where Tm³⁺ and Er³⁺ bands appear in the visible and NIR range.^52,53 The ET scheme and UC mechanisms for 980 nm excitation are shown in Fig. SI6.† A very weak Nd³⁺ emission is also observed at around 850 nm (see Fig. 2) which could be explained by the Er³⁺ → Nd³⁺ ET (see Fig. SI6†), as previously reported,^54–56 as well as by a Yb³⁺ → Nd³⁺ ET process, as reported by Jaque et al.⁵⁷ The high intensity of the Tm³⁺ blue emission could potentially be harnessed to generate secondary photochemical processes.

Interestingly, upon 806 nm laser excitation, emission from Tm³⁺ ions is not observed, but only bands due to Er³⁺ ions are present (see Fig. 3).

A schematic of the UC mechanisms upon 806 nm excitation, which involve energy transfer upconversion (ETU) and excited state absorption (ESA)⁵⁸ for the outer shells, is proposed in Fig. SI7.† It is worth noting that the Tm³⁺ ions in the core cannot be directly excited by 806 nm radiation, as evidenced by the lack of Tm³⁺ UC emission (Fig. 3). This proves the effectiveness of the optically inert second shell (doped with Y³⁺ ions) in avoiding ET processes between the external shells and the core of the MNPs.

NIR Stokes emission

Upon excitation at 806 nm, Nd³⁺ ions, especially those present in the 3^rd shell (22% Nd³⁺ ion concentration), act as efficient energy harvesters. Then, the absorbed energy is transferred to the Yb³⁺ ions in the 2^nd shell through a Nd³⁺ → Yb³⁺ ET process. It is known that a high Nd³⁺ concentration in fluoride hosts can efficiently quench the Nd³⁺ NIR emission through cross-relaxation and non-radiative de-excitation processes.⁵⁹ Therefore, the 2^nd shell of the MNPs was doped with a 1% concentration of Nd³⁺ ions to guarantee a good NIR Nd³⁺ emission intensity. The emission spectra at 20 °C for the MNPs upon 806 nm excitation are shown in Fig. 4.

Notable, temperature variations are not observed for the water colloids (1 wt%) upon CW 806 nm laser excitation for the time needed to acquire the spectrum. From the NIR emission spectra (Fig. 4), it can be observed that the presence of Er³⁺ ions in the 2^nd shell significantly affects relative emissions of the Nd³⁺ and Yb³⁺ ions. Particularly, the Yb³⁺/Nd³⁺ intensity ratio strongly decreases as the Er³⁺ ion concentration increases. This is due to the increase in the Yb³⁺ → Er³⁺ ET process, which quenches the Yb³⁺ emission.

After excitation, the Nd³⁺ ions undergo non-radiative relaxation to the lower lying ⁴F_3/2 level, in which the Nd³⁺ → Yb³⁺ and Yb³⁺ → Er³⁺ ET processes can take place (see UC emission of Er³⁺ ions in Fig. 3).

As shown in Fig. 4, the decrease in Yb³⁺ emission intensity with respect to Nd³⁺ emission intensity clearly indicates that the Yb³⁺ → Er³⁺ ET process becomes increasingly prominent as the Er³⁺ concentration in the second shell of the MNPs increases.

NIR thermometry

The capabilities of the present MNPs as luminescent NTs in the II-BW were investigated by analyzing the variation in their NIR emission spectra in the physiological temperature range. The Stokes emission in the NIR range upon 806 nm excitation of the MNPs were measured in the 20–50 °C temperature range, as shown in Fig. 5 for the 0% and 2% Er³⁺ MNPs (and in Fig. SI8† for the other MNPs). The emission spectra clearly show that the Yb³⁺/Nd³⁺ emission intensity ratio significantly decreases with an increase in temperature. Since the thermometric properties arise from a decrease in the Yb³⁺ emission intensity with respect to the Nd³⁺ emission intensity, we define the fluorescence intensity ratio (FIR) as follows:

	(1)

where, A_Yb and A_Nd are the integrated areas for the Yb³⁺ and Nd³⁺ emission, respectively. The areas were evaluated by integrating the emission signal over a suitable integration range (shaded areas in Fig. 5) for the Yb³⁺ (around 980 nm) and the Nd³⁺ (around 1060 nm) emissions. These bands were chosen due to their higher emission intensities than the Nd³⁺ intensity at 870 nm and the Yb³⁺ intensity at 1010 nm (see Fig. 4 and 5), while the integration range was considered in order to avoid the overlap of emission bands of Nd³⁺ and Yb³⁺ ions.

Fig. 6a shows the normalized FIR(Yb,Nd) behaviour as a function of temperature for all the MNPs. In all cases, the FIR values decrease almost linearly with temperature. The temperature dependence of the Yb³⁺/Nd³⁺ emission ratios was found to follow different trends for different compounds in the literature. As an example, for LiLa_0.9−xNd_0.1Yb_xP₄O₁₂ NPs, the Yb³⁺/Nd³⁺ emission ratio increases with an increase of temperature in the 300–400 K range.⁶⁰ On the other hand, the behaviour for the present MNPs is similar to that found by Ximendes et al. for Nd³⁺,Yb³⁺ doped LaF₃ NPs.⁶¹ It should be noted that since the Yb³⁺ emission arises because of a non-resonant ET from Nd³⁺ to Yb³⁺ ions (see Fig. SI7†), a phonon assisted mechanism has to be active, as described by the Miyakawa–Dexter (MD) model.⁶² Nonetheless, besides the direct Nd³⁺ → Yb³⁺ ET, a back ET Nd³⁺ ← Yb³⁺ process could occur^57,63 due to the thermal population of the highest Stark states of the ²F_5/2 level of the Yb³⁺ ions (shown in Fig. SI9†). Therefore, for the MNPs with no Er³⁺ ions in their 2^nd shell (Fig. 5a), the slight decrease in Yb³⁺ emission as temperature increases depends only on a subtle balance between these two processes. On the other hand, as shown in Fig. 5b, Fig. SI8† and Fig. 6a, the presence of Er³⁺ strongly decreases the Yb³⁺ emission intensity. Therefore, different ET mechanisms that influence the Yb³⁺ emission must take place.

In order to explain the Yb³⁺ temperature dependent behaviour due to the presence of Er³⁺ ions, Fig. 7 presents a schematic illustration of the possible ET processes that can take place among the Nd³⁺, Yb³⁺ and Er³⁺ ions. The energy levels for the Yb³⁺ ions were designed considering the absorption and emission spectra of the prepared MNPs without Er³⁺ ions in their 2^nd shell (see Fig. SI9†) and according to Falin et al.⁶⁴ In Fig. 7, the ⁴I_11/2 level structure is deduced from the absorption spectrum reported by Liu et al. for an Er³⁺ doped SrF₂ single crystal⁶⁵ while the ⁴I_15/2 Stark levels are from Carnall et al. for LaF₃:Er³⁺ crystals.⁶⁶

As shown in Fig. 7, due to the Kramers degeneracy, three and four Stark energy levels are expected for the ²F_5/2 and ²F_7/2 excited and ground levels of the Yb³⁺ ion, respectively.⁶⁴ The Nd³⁺ → Yb³⁺ ET process populates the highest Stark levels of the ²F_5/2 multiplet of Yb³⁺ ions, followed by non-radiative relaxation to the lower-lying Stark level of the ²F_5/2 multiplet and in turn by the radiative emission at 980 nm and 1010 nm. Due to Kramers degeneracy, the ⁴I_15/2 ground state of Er³⁺ ions is split into eight Stark levels. As reported by Liu et al.⁶⁵ for Er³⁺ doped SrF₂, the Er³⁺ ion absorption spectrum shows two main bands. The band at 970 nm is due to a transition from the lowest Stark level of the ⁴I_15/2 ground state to the lowest Stark levels of the ⁴I_11/2 multiplet. Moreover, the other band at 980 nm can be assigned to the transition starting from a higher energy (around 100 cm⁻¹) Stark level of the ⁴I_15/2 multiplet. Furthermore, other less intense bands are also observed at around 1000 nm due to lower energy transitions involving other ⁴I_11/2 and ⁴I_15/2 Stark levels. Therefore, there is an overlap between the Yb³⁺ emission (Fig. SI9†) and Er³⁺ absorption in the range of 980–1010 nm. On increasing the temperature, the population of the higher energy Stark levels of the ⁴I_15/2 ground state increases, making the resonant ET processes more efficient because the overlap between the Er³⁺ ions absorption and Yb³⁺ emission increases (see Fig. 7). Therefore, it is reasonable that the population of the ²F_5/2 level of the Yb³⁺ ions decreases; therefore the emission at 980 nm also weakens on increasing the temperature. The decrease in FIR(Yb,Nd) vs. temperature can therefore be explained by the decrease in the population of the lowest ²F_5/2 Stark level of Yb³⁺. In principle, this mechanism could be proven by considering that the population of the ⁴I_13/2 level, which is fed by non-radiative processes due to water phonons from the upper lying ⁴I_11/2 level, would increase due to the increase in the ⁴I_11/2 level population with temperature. Therefore, an increase in the 1.5 μm emission intensity of the Er³⁺ ions (due to the ⁴I_13/2 → ⁴I_15/2 transition) would be expected. Nonetheless, an increase in temperature also enhances the non-radiative depopulation of the ⁴I_11/2 level and therefore increases the 1.5 μm emission intensity, as described by Skripka et al.⁶⁷ Thus, it would be difficult to evaluate the contribution of each mechanism. The scheme described in Fig. 7 can also explain the behaviour of FIR(Yb,Nd) vs. temperature for the MNPs doped with different Er³⁺ concentrations. The increase in Er³⁺ concentration increases the Yb³⁺ → Er³⁺ ET, thus quenching the 980 nm emission due to Yb³⁺ ions. It should be noted that the FIR variation increases from 5% for MNPs with no Er³⁺ doping to 33% for MNPs doped with 8% Er³⁺. This enhancement in the FIR variation strongly affects the thermometric performance of the MNPs.

The relative thermal sensitivity, S_rel, is the commonly accepted parameter for direct comparison of various nanothermometers, particularly those with different Ln ion doping concentrations.

S _rel is defined as:^68–70

	(2)

where, T represents temperature.

Fig. 6b shows that the S_rel values increase when the Er³⁺ concentration increases. It can be noted that for the MNPs with a lower or 0% Er³⁺ concentration, S_rel is almost constant or shows only a slight temperature dependent variation. For the MNPs with a higher Er³⁺ doping, S_rel tends to increase as temperature increases. The S_rel values were estimated to be around 1.8 × 10⁻³ °C⁻¹ for the MNPs with 0% Er³⁺, whereas for the MNPs with 8% Er³⁺, the S_rel value significantly increased on increasing the temperature from (10.8 ± 0.8) × 10⁻³ °C⁻¹ at 20 °C to (16.2 ± 1.2) × 10⁻³ °C⁻¹ at 50 °C. It is clear that the presence of Er³⁺ in the 2^nd shell strongly improves the relative thermal sensitivity, based on FIR(Yb,Nd). It must be emphasized that efficient Yb³⁺ → Er³⁺ ET is beneficial for the thermometric properties, which remarkably increases the S_rel value when only Yb³⁺ and Nd³⁺ are doped in the 2^nd shell.

A comparison between the MNPs thermometric performance and the most recently investigated Nd³⁺ or Nd³⁺/Yb³⁺-based NTs in the literature is reported in Table 1. While the relative sensitivities of the MNPs with 0% Er³⁺ are similar to those reported in the literature for Nd³⁺ activated NPs, the S_rel values for the 8% Er³⁺ MNPs are among the highest reported for NIR-to-NIR NTs operating in the II-BW in water colloidal dispersions based on a single multishell-structured host (SrF₂ in the present investigation). Higher thermal sensitivity was determined in hybrid nanostructures consisting of NaGdF₄:Nd³⁺ NPs and PbS/CdS/ZnS quantum dots encapsulated in poly(lactic-co-glycolic) acid (PLGA), which had a S_rel of 2.5 × 10⁻² °C⁻¹.⁶⁹ Nonetheless, the present MNPs are much smaller (around 25 nm) than the abovementioned PLGA nanostructures (around 150 nm) and therefore they could be more useful in applications where nanoparticle size is a limiting issue, such as in the biomedical field.

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One of the most relevant parameters to describe the thermometric performance is the temperature uncertainty, δT, which defines the achievable precision of the temperature evaluation in the local environment in which the thermometer is working for a given optical setup.

This important parameter is defined as:³¹

	(3)

where, ΔFIR/FIR is the relative uncertainty of the thermometric parameter (in our case, FIR(Yb,Nd)). It is important to note that ΔFIR/FIR depends on the measurement setup and particularly on the signal to noise ratio of the measured signal.

Considering the FIR(Yb,Nd) values and their corresponding errors, the δT values were evaluated and shown in Fig. 8. The temperature uncertainties decrease as the Er³⁺ concentration increases, except for the 8% Er³⁺ MNPs, similarly to the 4% sample. This could be due to the worse signal to noise ratio for the 8% Er³⁺ MNPs NIR emission since the Yb³⁺ emission is quenched by a high Er³⁺ concentration. Therefore, the relative uncertainty of FIR(Yb,Nd) increases, leading to worse temperature uncertainty, although the MNPs with 8% Er³⁺ present the highest S_rel among all the MNPs.

Fig. 8 shows that using the present acquisition conditions, the MNPs with lower Er³⁺ concentrations are more unreliable as NTs since the temperature uncertainty is too high, whereas for the 4% and 8% Er³⁺ MNPs it is around 1.7 °C. The minimum measurable δT could be further improved by refining the spectral acquisition in order to increase the signal to noise ratio, hence decreasing the relative uncertainty of the FIR values.

Conclusions

In summary, a thermometric investigation was carried out on MNPs, which confirmed that they could be useful as efficient NIR NTs based on their Yb³⁺ and Nd³⁺ emissions.

We proved that the thermometric performance of the MNPs can be tuned by changing the Er³⁺ concentration in the thermally active 2^nd shell. In particular, the thermal relative sensitivity increases by increasing the Er³⁺ concentration. The MNPs with 8% Er³⁺ in their second shell show a very high relative thermal sensitivity in the 20–50 °C temperature range, from (1.08 ± 0.08) × 10⁻² °C⁻¹ to (1.62 ± 0.12) × 10⁻² °C⁻¹. Although the MNPs with 8% Er³⁺ present the highest S_rel, the MNPs with 4% Er³⁺, which have an S_rel from (0.97 ± 0.05) × 10⁻² °C⁻¹ to (1.38 ± 0.07) × 10⁻² °C⁻¹, show the lowest minimum measurable temperature variation δT (around 1.7 °C) because of the lower error in FIR(Yb,Nd) due to the better signal-to-noise ratio in their NIR spectra with respect to the MNPs with 8% Er³⁺. Highlighting that the thermometry features for the MNPs were determined in water colloidal dispersion, the relative sensitivity values for the MNPs with the higher Er³⁺ concentrations are among the highest reported for water dispersible NIR-to-NIR NTs working in the II-BW based on a single NP.

The present nanosystems can be easily and efficiently dispersed in water and physiological solutions, which ensures their possible use in biomedicine. From the detailed spectroscopic investigation, we demonstrated that the MNPs are multifunctional platforms for possible use as diagnostic tools in bioimaging in the visible range and NIR in the II-BW with the possibility of double excitation in the I-BW at 980 and 800 nm within the same MNP.

The possibility of a multicolor UC emission was clearly demonstrated. In the NIR region, the MNPs exhibit a strong emission from Yb³⁺ and Nd³⁺ ions in the II-BW upon excitation at 806 nm. Moreover, the Yb³⁺/Nd³⁺ emission ratio appears to be strongly influenced by the presence of a third dopant ion (Er³⁺) in the 2^nd shell layer. Therefore, the MNPs are potential candidates as multimodal NTs for biomedicine.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

AS, PC and MP thank University of Verona for financial support in the framework of the “Ricerca di base” project. AB thanks the Canadian Institutes of Health Research – Breast Cancer Society of Canada (CIHR-BCSC), for the Postdoctoral Fellowship given to him through the Eileen Iwanicki Postdoctoral Fellowship on Breast Cancer Imaging. FV is grateful to both the Natural Sciences and Engineering Research Council (NSERC) of Canada and the Fonds de Recherche du Québec – Nature et technologies (FRQNT) for supporting his research.

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Footnotes

† Electronic supplementary information (ESI) available: X-ray patterns, DLS measurements, UC spectra, energy transfer schemes, thermometric measurements, Ytterbium absorption and emission spectra. See DOI: 10.1039/c7nr06141b

‡ Current address: Wageningen University & Research, Axis Y, Bornse Weilanden 9, 6708, Wageningen, The Netherlands.

§ Current address: BioNanoPlasmonics Laboratory, CIC biomaGUNE, Paseo de Miramón 182, Donostia.

¶ Current address: Department of Physics and CICECO – Aveiro Institute of Materials, University of Aveiro, 3810-193, Aveiro, Portugal.

This journal is © The Royal Society of Chemistry 2018