Upconversion nanoparticles (UCNPs) provide an ideal platform for achieving multifunction, such as multimodal imaging, sensing, therapy, etc., mainly by combining with other nanomaterials to construct complicated heterogeneous nanostructures. Multifunctional integration on a simple single-phase structure still is an open question and poses a big challenge. Here we show that small-sized NaGdF4:Yb3+, Er3+ UCNPs (~7.5 nm) can simultaneously possess upconversion luminescence (UCL), temperature sensing, paramagnetic and photothermal conversion properties, endowing them great potential for photothermal treatments with real-time imaging and temperature monitoring. Effects of Yb3+ concentrations, nanoparticle sizes and core/shell structures on the light-to-heat conversion capability of UCNPs were also investigated, and the results were discussed on the basis of the variation in absorption rates and non-radiative relaxation probabilities of UCNPs. There is a competition between UCL and light-to-heat conversion processes. Higher UCL efficiency and enhanced photothermal conversion properties can be realized on UCNPs with the active-core/active-shell structure due to enhanced absorption rates.
© 2015 Optical Society of America
Upconversion nanoparticles (UCNPs), that can emit visible light under near-infrared (NIR) excitation, have attracted great attention for their potential applications in a variety of fields, such as bioimaging, solar cells and 3D display [1–3 ]. Especially in the biomedical field, UCNPs exhibit many unique advantages over conventional downconversion counterparts, including high signal-to-noise ratios, low toxicity and radiation damage, good photostability, and improved tissue penetration depth . UCNPs also provide such an ideal platform for multifunctional integration, such as imaging, detection and therapy [4–7 ]. Modified by Gd3+ ions or labeled with 18F ions, multimodality imaging technologies have been confirmed on NaYF4:Yb3+, Er3+ UCNPs, including upconverison luminescence (UCL) imaging, X-ray computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) [4, 5 ]. Mesoporous or hollow upconversion nanospheres can be simultaneously used as imaging probes and drug carriers [6, 7 ]. Based on their temperature-sensitive fluorescence, UCNPs also can simultaneously realize cell imaging and nanoscale temperature sensing . In addition, UCNPs can integrate with magnetic nanoparticles or metal nanostructures to build multifunctional nanocomposites, which are able to utilize different properties of monomers and take advantage of their coupling effects [9, 10 ].
Multifunctional integration on single UCNPs will be very attractive for practical applications. Hexagonal (β) phase NaYF4:Yb3+, Er3+ UCNPs have been reported as the most efficient upconversion nanomaterials. However, their absolute quantum yields still remain low and are usually less than 1% . Most of absorption energy is lost as heat or by downconversion luminescence. Considering their unique upconversion and temperature-sensitive luminescence properties, if part of absorption energy of UCNPs is converted into heat efficiently, it can be expected that the multifunctional integration of UCL imaging, temperature sensing and photothermal conversion would be simply realized on single-phase nanoparticles.
Photothermal nanoparticles can realize precise and selective nanoscale heating, and show great potential for applications in various fields, from killing cancer cells and driving liquid flow in microfluidic chips to data savings and laser writing [11, 12 ]. Organic dye molecules, metal nanostructures, carbon nanomaterials and semiconductor quantum dots have been proposed as photothermal conversion materials [13–18 ]. Among them, metal nanostructures are especially ideal as photothermal conversion materials, owing to their strong absorption rates to visible or NIR light, tunable absorption bands and high photothermal conversion efficiencies. In the biomedical field, in order to reduce the radiation damage to normal cells and improve the tissue penetration depth, optical absorption bands of metal nanostructures should be in the transparent window of biological tissues (650-1350 nm) . By adjusting the length-to-radius ratio of Au nanorods or controlling the thickness of Au shells, their absorption bands can be shifted to the NIR light region. However, the sizes of such Au nanostructures normally are too large (>50 nm), which will bring the damage to biological tissues after accumulation in organs without fast clearance . Novel photothermal nanomaterials with intrinsic and fixed NIR absorption bands, such as CuS, Cu9S5 and LaB6 have been proposed [13, 14, 21 ]. In addition, integrating temperature reading and optical imaging features on photothermal nanoparticles will be very attractive, which can allow for real-time temperature monitoring, imaging guidance and dynamical control over treatment parameters. It is extremely beneficial for precise and controlled photothermal treatments. Though metal nanostructures can also be used for optical imaging, either via two-photon fluorescence or via surface plasma resonance (SPR) scattering, special light sources are needed, such as white light for SPR scattering and expensive pulse lasers for two-photon fluorescence imaging . Nanocomposites combining fluorescent or magnetic nanomaterials with metal nanoparticles are capable of achieving multifunctional integration. However, they normally suffer from time-consuming synthetic procedures, complex structures and larger sizes.
Lanthanide-doped nanoparticles have also been considered for photothermal therapies . Combining with their fluorescence properties, lanthanide-doped nanoparticles capable of efficient heat generation under illumination with laser radiation provide an alternative method to achieve multifunction at the same time on a single structure. The light-to-heat conversion ability has been demonstrated for Nd3+-activated downconversion luminescence nanoparticles . Compared with downcoversion counterparts, lanthanide-doped UCNPs would be a more attractive candidate capable of offering heating, tracking and temperature reading on a single structure, due to the fact that they can be effectively excited by the NIR light. Here, ultra-small NaGdF4:Yb3+, Er3+ UCNPs (~7.5 nm) were synthesized, and their photothermal conversion properties were validated along with excellent UCL, temperature sensing and paramagnetic properties. Influences of nanoparticle sizes, Yb3+/Er3+ concentrations and core/shell structures were also investigated and discussed.
2. Experimental methods
All the chemicals in the experiment were purchased from Sigma-Aldrich and used as received. UCNPs were synthesized according to a modification of the previously reported procedure using rare-earth acetates as precursors . In a typical synthesis of β-NaGdF4:0.2Yb3+, 0.02Er3+ nanoparticles, 1 mmol of rare-earth acetates (Gd/Yb/Er = 78:20:2) with 6 mL of oleic acid (OA) and 15 mL of 1-octadecene (ODE) were added to a 100 mL flask, and then heated to 100 °C for 30 min under vigorous stirring to form a clear solution. After cooling down to 50 °C, a methanol solution (20 mL) containing NH4F (4 mmol) and NaOH (2.5 mmol) was added. The resulting solution was kept at 50 °C for 30 min and then heated to 70 °C to evaporate methanol. In the following, the solution was heated to 305 °C under an argon atmosphere for 90 min and then cooled down to room temperature. The nanoparticles were precipitated by the addition of ethanol and isolated via centrifugation. The as-precipitated nanoparticles were washed several times with ethanol and dried in air at 70 °C overnight. UCNPs with various sizes were synthesized by using an identical procedure, except for the replacement of Gd3+ with Y3+ in the host materials.
For the synthesis of NaGdF4:Yb3+, Er3+@NaGdF4 UCNPs, 0.5 mmol of gadolinium acetate was added into 6 mL of OA and 15 mL of ODE and subsequently heated at 100 °C for 30 min to prepare the shell precursor solution. When the solution was cooled down to 50 °C, NaGdF4:Yb3+, Er3+ core nanoparticles (~0.7 mmol) in cyclohexane were added along with a methanol solution (10 mL) of NH4F (2 mmol) and NaOH (1.25 mmol). The resulting solution was stirred at 50 °C for 30 min and then heated to 305 °C for 90 min. After the solution was cooled down to room temperature, the obtained core/shell nanoparticles were collected and washed by the same procedure as that of core-only nanoparticles. A similar procedure was used to synthesize NaGdF4:Yb3+, Er3+@NaGdF4:0.4Yb3+ UCNPs, except that gadolinium and ytterbium acetates (Gd/Yb = 60:40) in OA and ODE were used as the growth solution for the active-shell preparation.
The nanoparticle morphology was observed on a Tecnai G2 transmission electron microscope (TEM). Powder X-ray diffraction (XRD) was performed on a Shimadzu XD-3A X-ray diffractometer equipped with a Cu Kα radiation (λ = 1.541 Å). For UCL spectra measurements, a continuous 975 nm diode laser was used as the excitation source. The laser beam was incident on a spot size of 5 mm in diameter through an optical fiber. The UCL signals were collected and analyzed by a portable spectrometer (Maya2000Pro, Ocean Optics Co.). A temperature-controlled heating system was used for temperature-dependent UCL spectra measurements. The solid powder samples were put into a copper sample cell, and a ceramic plate was placed below the sample cell for heating. The temperature was monitored by a thermocouple embedded on the copper surface near the sample cell. The heating plate and the thermocouple were connected to an intelligent PID regulator (LU-906M, Anthone Electronics Co. Ltd.) for precise temperature control.
Light-to-heat conversion properties of UCNPs both in dispersed solution and in solid powder state were studied. The dried nanoparticles were first pressed into the pellets with a thickness of 2 mm and a radius of 10 mm. For the heating effect measurements, the pellets were free-standing in air and irradiated by a 975 nm laser with a pump power of 0.5 W (power density: 2.55 W/cm2). The temperature of solid nanopowders was determined by their temperature-sensitive fluorescence. For measurements of the photothermal conversion performances of UCNPs in solution, the 975 nm laser (1.5 W) was delivered through a quantize cuvette containing the cyclohexane dispersion (2 ml) of UCNPs with a concentration of ~20 mg/mL (power density: 7.64 W/cm2). In order to record the temperature changes, a thermocouple with an accuracy of ± 0.1 °C was immersed in the solution perpendicular to the path of the laser. As the control experiments, the temperature changes of pure cyclohexane and the cyclohexane dispersion of undoped NaGdF4 nanoparticles were also measured.
3. Results and discussion
3.1. Structural characterization, UCL spectra and temperature sensing properties
The TEM image revealed that well-dispersed NaGdF4:Yb3+, Er3+ spherical nanoparticles were successfully synthesized [Fig. 1(a) ], with an average diameter of ~7.5 nm [inset of Fig. 1(a)]. Powder XRD patterns [Fig. 1(b)] conformed that the obtained UCNPs were of pure β-NaGdF4 phase (JCPDS 27-0699), and no secondary phase could be detected.
The visual photography of UCNPs dispersed in cyclohexane displayed a green color under the irradiation of a 975 nm diode laser [inset of Fig. 2(a) ]. UCL spectra of UCNPs at various temperatures were also measured [Fig. 2(a)]. At room temperature, three main emission peaks at ~525, 545 and 655 nm were observed, which are assigned to the 2H11/2→4I15/2, 4S3/2→4I15/2, and 4F9/2→4I15/2 transitions of Er3+ ions. With increasing temperature from 30 to 100 °C, the overall UCL intensity increased for three emission bands. This abnormal temperature-dependence of UCL has been reported and the cause of it has been discussed in our previous paper . It could also be found the 525 nm (2H11/2→4I15/2) emission band showed a more significant increase in intensity with temperature than the 545 nm (4S3/2→4I15/2) band. This is because a thermal equilibrium exists between the 2H11/2 and 4S3/2 energy levels of Er3+ ions, owing to the narrow energy gap between them. According to Boltzmann’s distribution, the intensity ratio (IH/IS) between the 2H11/2→4I15/2 and 4S3/2→4I15/2 transitions as a function of temperature can be expressed as :
Where, C is a constant, ΔE is the energy gap separating two excited states, k is the Boltzmann constant, and T is the absolute temperature. Figure 2(b) shows the temperature dependence of ln(IH/IS) on the inverse temperature 1/T. In accordance with Eq. (1), a good linear fitting (lnIH/IS = 1.65-782.6/T) was obtained. This demonstrates that NaGdF4:Yb3+, Er3+ UCNPs can be used as remote temperature sensing probes, by monitoring the intensity ratios of 525 and 545 nm emission bands. Though for bio-applications the use of visible emissions for thermal sensing is restricted by tissue absorption at those wavelengths, this fluorescence intensity ratio technology provides a promising non-contact temperature sensing method with high sensitivity and less environmental dependence.
The thermal sensitivity of UCNPs can be defined as :
According to Eq. (2), the thermal sensitivity of UCNPs is directly related to the energy separation ΔE , and depends on the temperature T. The maximum sensitivity value of NaGdF4:Yb3+, Er3+ UCNPs is about 0.0042 K−1, which is close to the previously reported value (~0.0048 K−1) in Er3+-doped oxides . A heating-cooling cycle was performed and a good repeatability was obtained in the temperature range of 25–120 °C.
3.2 Photothermal conversion and paramagnetic properties
We first investigated the photothermal conversion properties of NaGdF4:Yb3+, Er3+ solid powders by exposing to the 975 nm laser with a pump power of 0.5 W. The temperatures rise was evaluated by applying Eq. (1) and the above experimental values of C and ΔE/k. Under the irradiation of the 975 nm light for 15 s, the temperature of the exposed area rapidly increased to 173 °C, and to 218 °C for 1 min [Fig. 2(b)]. It proves that NaGdF4:Yb3+, Er3+ UCNPs exhibit a good light-to-heat conversion capability. In NaGdF4:Yb3+, Er3+, the excitation light (~975 nm) is mainly absorbed by Yb3+ ions, which have an extinction coefficient 10-fold larger than Er3+ ions. Part of absorption energy can be successive transferred to Er3+ ions, leading to the UCL in visible range via the multiphoton mechanism. Due to the limited UCL efficiency of about a few percent for UCNPs, the major part of the absorbed energy is released in the form of the downconversion luminescence of Yb3+ or Er3+ ions and the non-radiative relaxation. Non-radiative transitions, between various excited states of Er3+ ions or directly across energy gaps of excited and ground states of Yb3+ or Er3+ ions, are involved with phonon creation, resulting in the heat generation in UCNPs. We also examined the temperature rise of NaGdF4:Yb3+, Er3+ UCNPs in cyclohexane solution. Under the irradiation of 975 nm laser with the power of 1.5 W, the control experiment showed that the temperature rise of the pure cyclohexane and the cyclohexane containing no-doping NaGdF4 nanoparticles was negligible (<1 °C). For the cyclohexane dispersion of NaGdF4:Yb3+, Er3+ UCNPs, the temperature could be increased by ~5 °C [Fig. 2(c)]. Several heating cycles were performed and a good repeatability was obtained. Also, no obvious changes in the morphology of UCNPs could be observed after the heating cycles.
Besides the UCL, temperature sensing and light-to-heat conversion properties, NaGdF4:Yb3+, Er3+ UCNPs also exhibited paramagnetic properties due to the large magnetic moment of Gd3+ ions [Fig. 2(d)]. The magnetic mass susceptibility of the as-prepared nanoparticles is ~7.61 × 10−5 emu g−1 Oe−1, which is close to the previously reported value of Gd3+-doped fluoride nanoparticles . It indicates that NaGdF4:Yb3+, Er3+ UCNPs may also have promising potential applications in bio-separation and magnetic resonance imaging.
All the above results imply that NaGdF4:Yb3+, Er3+ UCNPs would be an ideal multifunctional platform, which is able to integrate optical/magnetic imaging, temperature sensing and photothermal treatments on single nanoparticles with small sizes (<10 nm). In comparison with other photothermal conversion materials, NaGdF4:Yb3+, Er3+ UCNPs show great potential especially for controlled and localized heating of targets with real-time temperature reading and imaging guidance. It is worth pointing out that the absorption of 980nm light by the water component in biological samples may induce potential thermal damages to normal cells and tissues [29, 30 ], especially when long-duration or high-power-density laser exposure is needed. Therefore, effects of Yb3/Er3+ concentrations, particle sizes and core/shell structures were investigated to further improve the photothermal conversion properties of UCNPs.
3.3 Effects of Yb3+ and Er3+ concentrations
Influences of Yb3+ and Er3+ concentrations on the UCL and light-to-heat conversion properties of NaGdF4:Yb3+, Er3+ UCNPs were investigated. As shown in Fig. 3(a) , the photothermal conversion capability of NaGdF4:Yb3+, Er3+ obviously depends on the Yb3+ concentrations. The temperature change goes up with increasing Yb3+ concentrations in NaGdF4:Yb3+, Er3+ UCNPs. For example, the cyclohexane dispersion of NaGdF4:0.4Yb3+, Er3+ UCNPs exhibited a temperature rise of ~10 °C under the irradiation of 975 nm laser over a period of 9 min. Unfortunately, as the Yb3+ concentrations are higher than 20 mol%, the UCL intensity starts to decrease [Fig. 3(b)] due to the concentration quenching between Yb3+ ions. A balance between the UCL efficiency and the heat generation ability need to be considered. It is known that Yb3+ concentrations determine the absorption rate to the NIR light in Yb3+/Er3+ co-doped UCNPs. At higher Yb3+ concentrations, more excitation energy can be absorbed and released in heat, leading to the increased heat generation capability. It was found that Er3+ concentrations had slight influences on the temperature rise of the cyclohexane dispersion of NaGdF4:Yb3+, Er3+ UCNPs. Moreover, excess Er3+ ions (>2 mol%) would also induce the decrease of UCL intensities.
3.4 Effects of nanoparticle sizes
We further investigated the influences of nanoparticle sizes on the photothermal conversion properties. UCNPs with different sizes were prepared by adjusting Gd/Y ratios in the Na(Gd,Y)F4 host. For NaYF4-based UCNPs, Gd3+ doping has proved to be an effective method to reduce the nanoparticle size [3, 31 ]. This reduction in size is attributed to the increases in surface charge density of nanocrystals after Gd3+ doping, which slows the diffusion of F- ions to the nanocrystal surface in growth solution . TEM images showed that with decreasing Gd3+ contents from 78 to 0 mol% in Na(Gd,Y)F4: Yb3+, Er3+, the nanoparticle size increased from 7.5 to 22.4 nm [Figs. 1(a) and 4(a)–4(c) ], where the Yb3+ and Er3+ concentrations were fixed at 20 and 2 mol%, respectively. XRD measurements indicated that all the UCNPs with various sizes exhibited a pure hexagonal phase. With the increase of nanoparticle sizes, the temperature changes of the cyclohexane dispersion of UCNPs over a certain period became smaller under the 975 nm laser irradiation [Fig. 4(d)]. The solid-state samples showed a similar trend.
As mentioned above, the absorbed energy by UCNPs is converted into phonon emissions, upconversion and downconversion luminescence, respectively. Due to the enhanced surface quenching effects, smaller nanoparticles have higher non-radiative transition rates and show a more effective heat generation capability, at the expense of weaker emissions including downconversion and upconversion luminescence [Fig. 4(e)].
3.5 Effects of core/shell structures
Increasing the absorption rate by doping more Yb3+ ions or enhancing the non-radiative relaxation by reducing the nanoparticle size can improve the light-to-heat conversion capability of UCNPs, however, both of these technologies unavoidably induce the decrease of the UCL efficiency at the same time. To simultaneously obtain higher heating and UCL efficiencies, UCNPs with various core/shell structures were synthesized and investigated. There are two types of shell composition, one is the inert shell that has no Yb3+ doping and can protect the luminescent core from the luminescence quenching caused by surface defects and ligands. The other is the active shell that contains Yb3+ ions and can increase the absorption rate to the NIR light besides protecting the core . Figure 5 shows TEM images of NaGdF4:Yb3+, Er3+/NaGdF4 active-core/inert-shell and NaGdF4:Yb3+, Er3+/NaGdF4: 0.4 Yb3+ active-core/active-shell UCNPs. After the shell growth, the nanoparticle sizes increased to ~11.7 nm for active-core/inert-shell UCNPs, and to ~12.1 nm for active-core/active-shell ones. The increase in the particle size suggests that the shell with a thickness of ~2 nm has been successfully grown around the core.
Figure 6 shows the UCL spectra and heating effects of core/shell structured UCNPs. Compared with the core-only nanoparticles, an obvious UCL enhancement could be observed after the NaGdF4 or NaGdF4:40% Yb3+ shell growth [Fig. 6(a)], suggesting that coating a shell with a similar crystal lattice structure around the NaGdF4:Yb3+, Er3+ core can effectively minimize the luminescence quenching from surface defects and ligands. The further UCL enhancement of the active-core/active-shell nanoparticles is believed to be caused by energy transfer of excited Yb3+ ions in the active shell to the NaGdF4:Yb3+, Er3+ core . However, their photothermal conversion properties showed different trends compared with core-only NaGdF4:Yb3+, Er3+ UCNPs. The magnitude of the temperature increment of the inert-shell UCNPs in solution or solid state was smaller than that of core-only ones at the same conditions [Figs. 6(b) and 6(c)]. It could be attributed to the suppression of non-radiative relaxation associated with the surface quenching processes after the shell coating, and therefore less absorption energy was released in heat. It is worth noting that only a few percent of absorption energy is converted into visible photon emissions, and the increase in UCL efficiency should not have a huge effect on the light-to-heat conversion capability of UCNPs. Therefore, the smaller temperature rise of the inert-shell nanoparticles was related to the increase in the downconversion luminescence efficiency caused by the surface passivation effect. It also indicates that the photothermal properties of UCNPs can be further improved by suppressing their downconversion emissions in the NIR range.
Unlike the active-core/inert-shell structure, the active-core/active-shell architecture is more beneficial for obtaining satisfying UCL and photothermal conversion properties at the same time. As shown in Fig. 6, the active-shell could not only more significantly enhance the UCL of UCNPs but also increase their light-to-heat conversion capability. The laser-induced maximum temperature of the exposed area for the solid-state sample could be up to 244 °C [Fig. 6(c)]. The surface passivation effect still existed for the active-shell nanoparticles, the increase in light-to-heat conversion capability was ascribed to the enhanced absorption rate to the NIR light. Extra absorption by Yb3+ ions in the shell caused more optical radiation to be converted into heat at the same irradiation conditions.
Small-sized NaGdF4:Yb3+, Er3+ UCNPs with various doping concentrations, nanoparticle sizes and core/shell structures have been successfully synthesized. The UCL, temperature sensing, paramagnetic and photothermal conversion properties of these UCNPs have been studied. Increasing Yb3+ ions concentrations and decreasing the nanoparticle sizes can improve the photothermal conversion capability of UCNPs, due to enhanced absorption rates and non-radiative relaxation probabilities, respectively. However, these techniques also unavoidably lead to the decrease of the UCL intensities. Compared with the inert-shell, the active-shell coating cannot only improve the absorption rate to the 975 nm light but also suppress the surface quenching effect, and therefore can help to obtain satisfying UCL and light-to-heat conversion properties at the same time. The laser-induced temperature increase can be up to ~10 °C for the cyclohexane dispersion of UCNPs, and up to ~240 °C in solid powder state. Along with their excellent UCL, temperature sensing and paramagnetic properties, NaGdF4-based UCNPs may be used for local hyperthermal treatments of cells with imaging guidance and real-time temperature reading via a no-contact method. As a proof-of-concept experiment, here high-power excitation light is still needed to obtain the considerable temperature rise. Sustained efforts should be put in to improve their light-to-heat conversion capability, e. g., to increase the absorption rate of UCNPs by dye molecular modification, or to suppress the downconversion luminescence probability by suitable ion doping.
The work was financially supported by the National Natural Science Foundation of China (NSFC) (No. 51302038) and the Natural Science Foundation of Jiangsu Province of China (No. BK2012346). It is also partially supported by Jiangsu Key Laboratory For Advanced Metallic Materials (No. BM2007204).
References and links
3. F. Wang, Y. Han, C. S. Lim, Y. Lu, J. Wang, J. Xu, H. Chen, C. Zhang, M. Hong, and X. Liu, “Simultaneous phase and size control of upconversion nanocrystals through lanthanide doping,” Nature 463(7284), 1061–1065 (2010). [CrossRef] [PubMed]
4. Q. Liu, Y. Sun, C. Li, J. Zhou, C. Li, T. Yang, X. Zhang, T. Yi, D. Wu, and F. Li, “18F-labeled magnetic-upconversion nanophosphors via rare-earth cation-assisted ligand assembly,” ACS Nano 5(4), 3146–3157 (2011). [CrossRef] [PubMed]
5. A. Xia, M. Chen, Y. Gao, D. Wu, W. Feng, and F. Li, “Gd3+ complex-modified NaLuF4-based upconversion nanophosphors for trimodality imaging of NIR-to-NIR upconversion luminescence, X-Ray computed tomography and magnetic resonance,” Biomaterials 33(21), 5394–5405 (2012). [CrossRef] [PubMed]
6. J. W. Zhao, X. M. Liu, D. Cui, Y. J. Sun, Y. Yu, Y. F. Yang, C. Du, Y. Wang, K. Song, K. Liu, S. Z. Lu, X. G. Kong, and H. Zhang, “A facile approach to fabrication of hexagonal-phase NaYF4:Yb3+, Er3+ hollow nanospheres: formation mechanism and upconversion luminescence,” Eur. J. Inorg. Chem. 2010(12), 1813–1819 (2010). [CrossRef]
7. F. Zhang, G. B. Braun, A. Pallaoro, Y. Zhang, Y. Shi, D. Cui, M. Moskovits, D. Zhao, and G. D. Stucky, “Mesoporous multifunctional upconversion luminescent and magnetic “nanorattle” materials for targeted chemotherapy,” Nano Lett. 12(1), 61–67 (2012). [CrossRef] [PubMed]
8. F. Vetrone, R. Naccache, A. Zamarrón, A. Juarranz de la Fuente, F. Sanz-Rodríguez, L. Martinez Maestro, E. Martín Rodriguez, D. Jaque, J. García Solé, and J. A. Capobianco, “Temperature sensing using fluorescent nanothermometers,” ACS Nano 4(6), 3254–3258 (2010). [CrossRef] [PubMed]
9. C. Mi, J. Zhang, H. Gao, X. Wu, M. Wang, Y. Wu, Y. Di, Z. Xu, C. Mao, and S. Xu, “Multifunctional nanocomposites of superparamagnetic (Fe3O4) and NIR-responsive rare earth-doped up-conversion fluorescent (NaYF4 : Yb,Er) nanoparticles and their applications in biolabeling and fluorescent imaging of cancer cells,” Nanoscale 2(7), 1141–1148 (2010). [CrossRef] [PubMed]
10. B. Dong, S. Xu, J. Sun, S. Bi, D. Li, X. Bai, Y. Wang, L. P. Wang, and H. W. Song, “Multifunctional NaYF4:Yb3+, Er3+@Ag core/shell nanocomposites: integration of upconversion imaging and photothermal therapy,” J. Mater. Chem. 21(17), 6193–6200 (2011). [CrossRef]
12. A. Bednarkiewicz, D. Wawrzynczyk, A. Gagor, L. Kepinski, M. Kurnatowska, L. Krajczyk, M. Nyk, M. Samoc, and W. Strek, “Giant enhancement of upconversion in ultra-small Er³⁺/Yb³⁺:NaYF₄ nanoparticles via laser annealing,” Nanotechnology 23(14), 145705 (2012). [CrossRef] [PubMed]
13. Q. Tian, M. Tang, Y. Sun, R. Zou, Z. Chen, M. Zhu, S. Yang, J. Wang, J. Wang, and J. Hu, “Hydrophilic flower-like CuS superstructures as an efficient 980 nm laser-driven photothermal agent for ablation of cancer cells,” Adv. Mater. 23(31), 3542–3547 (2011). [CrossRef] [PubMed]
14. Q. Tian, F. Jiang, R. Zou, Q. Liu, Z. Chen, M. Zhu, S. Yang, J. Wang, J. Wang, and J. Hu, “Hydrophilic Cu9S5 nanocrystals: a photothermal agent with a 25.7% heat conversion efficiency for photothermal ablation of cancer cells in vivo,” ACS Nano 5(12), 9761–9771 (2011). [CrossRef] [PubMed]
16. I. H. El-Sayed, X. Huang, and M. A. El-Sayed, “Selective laser photo-thermal therapy of epithelial carcinoma using anti-EGFR antibody conjugated gold nanoparticles,” Cancer Lett. 239(1), 129–135 (2006). [CrossRef] [PubMed]
20. M. Longmire, P. L. Choyke, and H. Kobayashi, “Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats,” Nanomedicine (Lond.) 3(5), 703–717 (2008). [CrossRef] [PubMed]
21. C. J. Chen and D. H. Chen, “Preparation of LaB6 nanoparticles as a novel and effective near-infrared photothermal conversion material,” Chem. Eng. J. 180, 337–342 (2012). [CrossRef]
22. D. Jaque, L. Martínez Maestro, B. del Rosal, P. Haro-Gonzalez, A. Benayas, J. L. Plaza, E. Martín Rodríguez, and J. García Solé, “Nanoparticles for photothermal therapies,” Nanoscale 6(16), 9494–9530 (2014). [CrossRef] [PubMed]
23. A. Bednarkiewicz, D. Wawrzynczyk, M. Nyk, and W. Strek, “Optically stimulated heating using Nd3+ doped NaYF4 colloidal near infrared nanophosphors,” Appl. Phys. B 103(4), 847–852 (2011). [CrossRef]
25. D. D. Li, Q. Y. Shao, Y. Dong, and J. Q. Jiang, “Anomalous temperature-dependent upconversion luminescence of small-sized NaYF4:Yb3+, Er3+ nanoparticles,” J. Phys. Chem. C 118(39), 22807–22813 (2014). [CrossRef]
26. B. Dong, B. Cao, Y. He, Z. Liu, Z. Li, and Z. Feng, “Temperature sensing and in vivo imaging by molybdenum sensitized visible upconversion luminescence of rare-earth oxides,” Adv. Mater. 24(15), 1987–1993 (2012). [CrossRef] [PubMed]
28. S. J. Zeng, J. J. Xiao, Q. B. Yang, and J. H. Hao, “Bi-functional NaLuF4:Gd3+/Yb3+/Tm3+ nanocrystals: structure controlled synthesis, near-infrared upconversion emission and tunable magnetic properties,” J. Mater. Chem. 22(19), 9870–9874 (2012). [CrossRef]
29. L. M. Maestro, P. Haro-González, B. del Rosal, J. Ramiro, A. J. Caamaño, E. Carrasco, A. Juarranz, F. Sanz-Rodríguez, J. G. Solé, and D. Jaque, “Heating efficiency of multi-walled carbon nanotubes in the first and second biological windows,” Nanoscale 5(17), 7882–7889 (2013). [CrossRef] [PubMed]
30. P. Haro-González, W. T. Ramsay, L. Martinez Maestro, B. del Rosal, K. Santacruz-Gomez, M. C. Iglesias-de la Cruz, F. Sanz-Rodríguez, J. Y. Chooi, P. Rodriguez Sevilla, M. Bettinelli, D. Choudhury, A. K. Kar, J. G. Solé, D. Jaque, and L. Paterson, “Quantum dot-based thermal spectroscopy and imaging of optically trapped microspheres and single cells,” Small 9(12), 2162–2170 (2013). [CrossRef] [PubMed]
31. H. Na, K. Woo, K. Lim, and H. S. Jang, “Rational morphology control of β-NaYF4:Yb,Er/Tm upconversion nanophosphors using a ligand, an additive, and lanthanide doping,” Nanoscale 5(10), 4242–4251 (2013). [CrossRef] [PubMed]
32. F. Vetrone, R. Naccache, V. Mahalingam, C. G. Morgan, and J. A. Capobianco, “The active-core/active-shell approach: a strategy to enhance the upconversion luminescence in lanthanide-doped nanoparticles,” Adv. Funct. Mater. 19(15), 2424–2429 (2009).