Physiological Temperature Range Research Articles

Rational Design of a Nd3+‐Mn4+ Co‐doped Luminescent Thermometer: Towards High‐Sensitivity Temperature Sensing

AbstractHigh temperature sensitivity is an important development direction for luminescent thermometers, especially in the physiological temperature range. Herein, neodymium(III) and manganese(IV) ions were co‐doped into a yttrium gallium garnet host (YGG) and the relevant dopant concentrations were optimized in detail. The temperature‐dependent spectral survey indicates that when the temperature was above 240 K, the 2Eg→4A2g transition of Mn4+ and the 4F5/2→4I9/2 emission of Nd3+ show strong fluorescence quenching and gradual fluorescence enhancement, respectively. Such an apparent contrast mainly originates from the nonradiative cross‐relaxation between 2Eg (or 4T2g) and 4A2g states of Mn4+ and thermal coupling between the 4F5/2 and 4F3/2 levels of Nd3+, respectively. The obvious difference in fluorescence between the two luminescent ions leads to an excellent temperature sensing performance. The obtained relative sensitivity shows a maximum value at 280 K (7.90 % K−1) and maintains a magnitude above 5.00 % K−1 over the whole physiological temperature range. Moreover, the related temperature uncertainties are below 0.1 K from 298 K to 323 K, and the repeatability capability is larger than 98 %. The findings in this study offer a feasible approach to promote the sensing capability of temperature sensors by rationally designing co‐doping systems.

Multifunctional up/down-conversion luminescence of core/shell nanocomposite for self-monitored heating and fluorescence imaging

The simultaneous realization of real-time thermal sensing at physiological temperature range and fluorescence imaging during photothermal therapy (PTT) via single-component biocompatible nanocomposite could furthest avoid collateral damage and enhance phototherapeutic effect, which, up to now, is of great interest and still in a formidable challenge. Under near-infrared (NIR) light irradiation, Nd3+-doped nanoparticles (NPs) have emerged as candidates with outstanding properties such as down-conversion emissions in biological window (BW) and capable of light-to-heat conversion. However, these two properties associated with Nd3+ doping concentrations induce opposite changing trend and difficult to combine within one single nanocomposite. In this work, for breaking through the obstacles, core/shell NaLuF4:1%Nd@NaLuF4@NaLuF4:15%Yb,3%Er@NaLuF4:15%Yb@NaLuF4:85%Nd 808 nm light-triggered co-enhancement up/down-conversion luminescence (UCL/DCL) nanocomposite was purposely designed with efficient heating, thermal sensing and fluorescence imaging concurrently. The core emits high quantum yield (QY) DCL in BW while the outermost layer could convert the absorbed photon into thermal energy and also transfer a fraction of energy inwards to internal layer with exciting the UCL (Nd→Yb→Er) for thermal sensing via thermally coupled levels 2H11/2/4S3/2 of Er using the fluorescence intensity ratio (FIR) method. The simultaneously enhanced UCL/DCL and thermal effect in the engineered nanocomposite are satisfactorily realized due to suppressing the interionic quenching owing to the inert two layers NaLuF4 and NaLuF4:15%Yb. Such smart designed nanocomposite has potential application on PTT-based noninvasive cancer therapy.

Thermodynamics of transfer and partition of 3,5-diamino-1-phenyl-1,2,4-triazole in the 1-octanol/water biphasic system

In this paper, we focus for the first time on thermodynamics of transfer of 3,5-diamino-1-phenyl-1,2,4-triazole (DAPT) from water to liquid 1-octanol which is considered in pharmaceutical chemistry as an appropriate model of a lipid-like environment for studying a passive membrane transport of various drugs. The enthalpies of solution of DAPT have been determined calorimetrically in both solvents at 298.15, 308.15 and 328.15 K. The partition coefficients (P) have been obtained in the 1-octanol/water biphasic system at 298.15 and 328.15 K using a classical isothermic saturation method. Standard thermodynamic functions of DAPT transfer from water to a lipid-like phase have been calculated via the Gibbs–Helmholtz equation using the temperature dependence of the standard enthalpies of solution and the partition coefficient at the reference temperature of 298.15 K. We have found that the enthalpic term favours the solute transfer both at lower and elevated temperatures, whereas the entropic one contributes in the opposite manner. The free energy of transfer remains negative for all the temperature range studied indicating rather appreciable affinity of a potential drug towards a lipid-like environment. The comparison of the experimental and calculated P values indicates that our approach is able to predict with a good accuracy the behaviour of the 1,2,4-triazole derivatives for the physiological temperature range.

Temperature Sensing Based on Thermal Population of Low-Lying 7F Levels of Trivalent Europium ions in GdVO4

Temperature sensing performance of GdVO 4 : Eu 3+ phosphors have been studied using a method based on thermal coupling of the low-lying levels ( 7 F J : J = 0, 1, 2) of Eu 3+ . GdVO 4 : Eu 3+ phosphors exhibit the outstanding luminescence characteristics with temperature and high detection sensitivity. Luminescence intensity ratio has been investigated between the 5 D 0 → 7 F 4 emission intensities when 5 D 0 excited from thermally populated low-lying excited states 7 F 1 and 7 F 2 with respect to 7 F 0 level. The luminescence intensity ratio monotonously increases with rising of temperature from 133 K to physiological temperature of 313 K. Specifically, the maximum value of relative sensitivity S R reach to 6.73% K −1 for first scheme and 2.87% K −1 for second scheme. The GdVO 4 :Eu 3+ phosphor shows the excellent relative sensitivity of 1.23% K −1 in physiological temperature range (310 K), recommending its potential for applications in bio-medical field. • Temperature sensing via thermal coupling of the low-lying levels ( 7 F J : J = 0, 1, 2) of Eu 3+ . • GdVO 4 :Eu 3+ phosphors were prepared through high temperature solid state method. • The maximum value of relative sensitivity S R reach to 6.73 % K -1 for first scheme. • Excellent relative sensitivity of 1.23 % K -1 in physiological temperature range (310 K).

Terbium(III)-thiacalix[4]arene nanosensor for highly sensitive intracellular monitoring of temperature changes within the 303\u2013313\xa0K range

The work introduces hydrophilic PSS-[Tb2(TCAn)2] nanoparticles to be applied as highly sensitive intracellular temperature nanosensors. The nanoparticles are synthesized by solvent-induced nanoprecipitation of [Tb2(TCAn)2] complexes (TCAn - thiacalix[4]arenes bearing different upper-rim substituents: unsubstituted TCA1, tert-buthyl-substituted TCA2, di- and tetra-brominated TCA3 and TCA4) with the use of polystyrenesulfonate (PSS) as stabilizer. The temperature responsive luminescence behavior of PSS-[Tb2(TCAn)2] within 293–333 K range in water is modulated by reversible changes derived from the back energy transfer from metal to ligand (M* → T1) correlating with the energy gap between the triplet levels of ligands and resonant 5D4 level of Tb3+ ion. The lowering of the triplet level (T1) energies going from TCA1 and TCA2 to their brominated counterparts TCA3 and TCA4 facilitates the back energy transfer. The highest ever reported temperature sensitivity for intracellular temperature nanosensors is obtained for PSS-[Tb2(TCA4)2] (SI = 5.25% K−1), while PSS-[Tb2(TCA3)2] is characterized by a moderate one (SI = 2.96% K−1). The insignificant release of toxic Tb3+ ions from PSS-[Tb2(TCAn)2] within heating/cooling cycle and the low cytotoxicity of the colloids point to their applicability in intracellular temperature monitoring. The cell internalization of PSS-[Tb2(TCAn)2] (n = 3, 4) marks the cell cytoplasm by green Tb3+-luminescence, which exhibits detectable quenching when the cell samples are heated from 303 to 313 K. The colloids hold unprecedented potential for in vivo intracellular monitoring of temperature changes induced by hyperthermia or pathological processes in narrow range of physiological temperatures.

Harnessing DNA for nanothermometry.

Temperature measurement at the nanoscale has brought insight to a wide array of research interests in modern chemistry, physics, and biology. These measurements have been enabled by the advent of nanothermometers, which relay nanoscale temperature information through the analysis of their intrinsic photophysical behavior. In the past decade, several nanothermometers have been developed including dyes, nanodiamonds, fluorescent proteins, nucleotides, and nanoparticles. However, temperature measurement using intact DNA has not yet been achieved. Here, we present a method to study the temperature sensitivity of the DNA molecule within a physiologic temperature range when complexed with fluorescent dye. We theoretically and experimentally report the temperature sensitivity of the DNA-Hoechst 33342 complex in different sizes of double-stranded oligonucleotides and plasmids, showing its potential use as a nanothermometer. These findings allow for extending the thermal study of DNA to several research fields including DNA nanotechnology, optical tweezers, and DNA nanoparticles.

Two ratiometric thermometry methods based on the interplay between Eu[formula omitted] and Eu[formula omitted] and single Eu[formula omitted] emissions on OH[formula omitted]-free low-silica calcium aluminosilicate glass

The constant demand to accurately measure the temperature sheds light on luminescent materials that have dependence on their thermodynamic quantities. Several materials have been applied as sensors to measure temperature for different applications, however, very few showed high precision and sensitivity. This work reports the Eu2+/Eu3+-doped low-silica calcium aluminosilicate glass as a potential candidate for high sensitive ratiometric thermometer. The glass was analyzed close to the physiological temperature range, between 288.15 – 333.15 K. Since this glassy matrix provides the presence of two europium valences, two different approaches are presented. The first takes into account the temperature dependence of 5D0→7F4 emission for two different excitation wavelengths, and the second one is based on the interplay between Eu2+ and Eu3+ emissions. Both ratiometric approaches presented high reproducibility and relative sensitivity values, from 1.2 to 1.6 %/K and from 0.75 to 0.95 %/K, for the first and second approach, respectively.

Accurate In Vivo Nanothermometry through NIR-II Lanthanide Luminescence Lifetime.

Luminescence nanothermometry is promising for noninvasive probing of temperature in biological microenvironment at nanometric spatial resolution. Yet, wavelength- and temperature-dependent absorption and scattering of tissues distort measured spectral profile, rendering conventional luminescence nanothermometers (ratiometric, intensity, band shape, or spectral shift) problematic for in vivo temperature determination. Here, a class of lanthanide-based nanothermometers, which are able to provide precise and reliable temperature readouts at varied tissue depths through NIR-II luminescence lifetime, are described. To achieve this, an inert core/active shell/inert shell structure of tiny nanoparticles (size, 13.5nm) is devised, in which thermosensitive lanthanide pairs (ytterbium and neodymium) are spatially confined in the thin middle shell (sodium yttrium fluoride, 1nm), ensuring being homogenously close to the surrounding environment while protected by the outmost calcium fluoride shell (CaF2 , ≈2.5nm) that shields out bioactive milieu interferences. This ternary structure enables the nanothermometers to consistently resolve temperature changes at depths of up to 4mm in biological tissues, having a high relative temperature sensitivity of 1.4-1.1% °C-1 in the physiological temperature range of 10-64°C. These lifetime-based thermosensitive nanoprobes allow for in vivo diagnosis of murine inflammation, mapping out the precise temperature distribution profile of nanoprobes-interrogated area.

Ornithine carbamoyltransferase from psychrophiles to thermophiles: structural evolution of catalytic fold to accommodate physiological diversity.

Here, we have analyzed the enzyme ornithine carbamoyltransferase (OCTase) in different classes of microorganisms belonging to psychrophiles, mesophiles and thermophiles. This OCTase catalyzes the formation of citrulline from carbamoyl phosphate (CP) and ornithine (ORN) in arginine biosynthesis pathway and has certain unique adaptations to regulate metabolic pathways in extreme conditions. The tertiary structure of OCTase showed two binding domains, the CP domain and ORN-binding domain at N and C terminals, respectively. We propose general acid-base catalysis in Pseudomonas gessardii between His259 and Asp220 in which later may act as a recipient of proton in the process. The comparative docking analysis showed that substrate-binding loops have been evolved to accommodate their lifestyles across the physiological temperature range where two substrates bind on two distinct loops in psychrophiles and mesophiles, whereas both the substrates bind on a single-substrate-binding loop in thermophiles and bring down the flexibility of the active site pocket to improve its evolutionary fitness.

Temperature does matter-an additional dimension in kinase inhibitor development.

Kinase inhibitors are a major focus in drug development. Recent work shows that subtle temperature changes in the physiologically relevant temperature range can dramatically alter kinase activity and specificity. We argue that temperature is an essential factor that should be considered in inhibitor screening campaigns. In many cases, high-throughput screening is performed at room temperature or 30°C, which may lead to many false positives and false negatives when evaluating potential inhibitors in the physiological temperature range. As one example, we discuss a new antimalaria compound that inhibits the highly temperature-sensitive kinase CLK3 (CDC2-like kinase 3) from Plasmodiumfalciparum.

Modulating mechanical stability of heterodimerization between engineered orthogonal helical domains

Mechanically stable specific heterodimerization between small protein domains have a wide scope of applications, from using as a molecular anchorage in single-molecule force spectroscopy studies of protein mechanics, to serving as force-bearing protein linker for modulation of mechanotransduction of cells, and potentially acting as a molecular crosslinker for functional materials. Here, we explore the possibility to develop heterodimerization system with a range of mechanical stability from a set of recently engineered helix-heterotetramers whose mechanical properties have yet to be characterized. We demonstrate this possibility using two randomly chosen helix-heterotetramers, showing that their mechanical properties can be modulated by changing the stretching geometry and the number of interacting helices. These helix-heterotetramers and their derivatives are sufficiently stable over physiological temperature range. Using it as mechanically stable anchorage, we demonstrate the applications in single-molecule manipulation studies of the temperature dependent unfolding and refolding of a titin immunoglobulin domain and α-actinin spectrin repeats.

Temperature-robust activity patterns arise from coordinated axonal Sodium channel properties.

Action potentials are a key component of neuronal communication and their precise timing is critical for processes like learning, memory, and complex behaviors. Action potentials propagate through long axons to their postsynaptic partners, which requires axons not only to faithfully transfer action potentials to distant synaptic regions but also to maintain their timing. This is particularly challenging when axons differ in their morphological and physiological properties, as timing is predicted to diverge between these axons when extrinsic conditions change. It is unknown if and how diverse axons maintain timing during temperature changes that animals and humans encounter. We studied whether ambient temperature changes cause different timing in the periphery of neurons that centrally produce temperature-robust activity. In an approach combining modeling, imaging, and electrophysiology, we explored mechanisms that support timing by exposing the axons of three different neuron types from the same crustacean (Cancer borealis) motor circuit and involved in the same functional task to a range of physiological temperatures. We show that despite substantial differences between axons, the effects of temperature on action potential propagation were moderate and supported temperature-robust timing over long-distances. Our modeling demonstrates that to maintain timing, the underlying channel properties of these axons do not need to be temperature-insensitive or highly restricted, but coordinating the temperature sensitivities of the Sodium activation gate time constant and the maximum Sodium conductance is required. Thus, even highly temperature-sensitive ion channel properties can support temperature-robust timing between distinct neuronal types and across long distances.

Deep-Tissue Temperature Sensing Realized in BaY2O4:Yb3+/Er3+ with Ultrahigh Sensitivity and Extremely Intense Red Upconversion Luminescence.

In this paper, BaY2O4:Yb3+/Er3+, a high efficient red upconversion (UC) material, is first utilized as an optical thermometer in the biological window, accomplished through the fluorescence intensity ratio (FIR) of thermally coupled Stark sublevels of 4F9/2 (FIR(654/663)). The maximum absolute sensitivity of FIR(654/663)) is 0.19% K-1 at 298 K, which is much higher than most previous reports about FIR-based temperature sensors located in the biological windows. More importantly, the groove of FIR(654/663) for thermometry is nicely located in the physiological temperature range, indicating its potential thermometry application value in biomedicine. Furthermore, a simply ex vivo experiment is implemented to evaluate the penetration depth of the red emission in biological tissues, revealing that a detection depth of 6 mm can be achieved without any effect on the FIR values of I654 to I663. Beyond that, the temperature sensing behaviors of the thermally coupled levels 2H11/2 and 4S3/2 (FIR(523/550)) are also investigated in detail. In the studied temperature range, the absolute sensitivity of FIR(523/550) monotonously increases with the rising temperature and reaches its maximum value 0.31% K-1 at 573 K. All the results imply that BaY2O4:Yb3+/Er3+ is a promising candidate for deep-tissue optical thermometry with high sensitivity.

"Dumb" pH-Independent and Biocompatible Hydrogels Formed by Copolymers of Long-Chain Alkyl Glycidyl Ethers and Ethylene Oxide.

The formation and rheological properties of hydrogels based on amphiphilic ABA triblock polyether copolymers are described, relying solely on the hydrophobic interaction of long-chain alkyl glycidyl ether (AlkGE)- based A-blocks that are combined with a hydrophilic poly(ethylene glycol) (PEG) midblock. Via anionic ring-opening copolymerization (AROP), ethylene oxide (EO) and long-chain alkyl glycidyl ethers (AlkGEs) were copolymerized, using deprotonated poly(ethylene glycol) (PEG) macroinitiators (Mn of 10, 20 kg mol-1). The polymerization afforded amphiphilic ABA triblock copolymers with molar masses in the range of 21-32 kg mol-1 and dispersities (Đ) of Đ = 1.07-1.17. Kinetic studies revealed random copolymerization of EO and AlkGE, indicating random spacing of the hydrophobic AlkGE units by polar EO units. Following this approach, the hydrophobicity of the apolar blocks of amphiphilic ABA triblock polyethers can be tailored. Detailed rheological measurements confirmed the successful formation of hydrogels at different pH values as a consequence of nonpolar interactions and alkyl chain crystallization. Hydrogel formation was also observed at different ionic strengths (i.e., varied salt concentration), based on the hydrophobic aggregates. This behavior is in contrast to other often-used supramolecular cross-linking strategies, such as Coulomb interactions, complexation, or hydrogen bonding. Micro-differential scanning calorimetry (μ-DSC) measurements of the hydrogels revealed crystalline hydrophobic domains with melting temperatures in the physiological temperature range. In 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide (MTT) assays, diblock copolymers possessing structural analogy to the triblock copolymers were studied to assess the general cytotoxicity of amphiphilic polyethers bearing long alkyl chains at the polyether backbone, using splenic immune cells. At intermediate polymer concentrations, no cytotoxic effects were observed. This indicates that long-chain alkyl glycidyl ethers are promising for the introduction of highly hydrophobic as well as crystalline motifs at the polyether backbone in hydrogels for biomedical purposes.

NIR to NIR luminescence thermometry in core/multishells-structured nanoparticles operating in the biological window

Optical thermometry via near-infrared (NIR) emitting luminescent nanoparticles has attracted a great deal of attention during the last few years. In particular, nanothermometers operating in the biological windows are being strongly demanded for biomedical applications. In this sense, Tm3+ emissions centered around 800 and 1800 nm were explored here for ratiometric thermometry. And a luminescent thermometer based on NaYbF4/NaYF4: Tm3+-Yb3+/NaYF4 core/shell/shell-structured nanoparticles is designed. Excited by 980 nm laser, saturated emissions from Tm3+: 3H4→3H6 (~800 nm: first biological window NIR-I) and Tm3+: 3F4→3H6 (~1800 nm: third biological window NIR-III) transitions are readily obtained owing to the efficient upconversion processes in the core/multishells nanoparticles, finally resulting in the same dependence of NIR emissions on the pumping power. Different thermal response between 800 and 1800 nm emissions of Tm3+ ions enables optical thermometry via ratiometric method. In the physiological temperature range, the relative sensitivity Sr and absolute sensitivity Sa achieved here are about 0.33% K−1 and 3.9% K−1, respectively, with a temperature uncertainty of 0.75 K. These results illustrate that the nanothermometer developed in this work would be promising candidate for optical temperature measurement in bio-fields.

A local α-helix drives structural evolution of streptococcal M-protein affinity for host human plasminogen.

Plasminogen-binding group A streptococcal M-protein (PAM) is a signature surface virulence factor of specific strains of Group A Streptococcus pyogenes (GAS) and is an important tight binding protein for human plasminogen (hPg). After activation of PAM-bound hPg to the protease, plasmin (hPm), GAS cells develop invasive surfaces that are critical for their pathogenicity. PAMs are helical dimers in solution, which are sensitive to temperature changes over a physiological temperature range. We previously categorized PAMs into three classes (I-III) based on the number and nature of short tandem α-helical repeats (a1 and a2) in their NH2-terminal A-domains that dictate interactions with hPg/hPm. Class II PAMs are special cases since they only contain the a2-repeat, while Class I and Class III PAMs encompass complete a1a2-repeats. All dimeric PAMs tightly associate with hPg, regardless of their categories, but monomeric Class II PAMs bind to hPg much weaker than their Class I and Class III monomeric counterparts. Additionally, since the A-domains of Class II PAMs comprise different residues from other PAMs, the issue emerges as to whether Class II PAMs utilize different amino acid side chains for interactions with hPg. Herein, through NMR-refined structural analyses, we elucidate the atomic-level hPg-binding mechanisms adopted by two representative Class II PAMs. Furthermore, we develop an evolutionary model that explains from unique structural perspectives why PAMs develop variable A-domains with regard to hPg-binding affinity.

The influence of host material on NIR II and NIR III emitting Ni2+-based luminescent thermometers in ATiO3: Ni2+ (A = Sr, Ca, Mg, Ba) nanocrystals

In this work we present for the first time the effective modulation of spectroscopic parameters of Ni2+ emission based luminescence nanothermometer (LNT). Emission of Ni2+ ions, highly susceptible to the local symmetry variations, can be easily modulated by the change of the crystal field strength of matrix. In this approach we proposed four ATiO3 perovskite nanocrystalline matrixes, namely SrTiO3, CaTiO3, MgTiO3, BaTiO3, in which the change of the crystal field strength is induced by the Ti4+ - O2− distance elongation. With the increase of this distance we achieved 500 nm spectral shift of Ni2+ emission maximum from 1200 nm for SrTiO3: Ni2+ up to 1700 nm for MgTiO3: Ni2+. Furthermore, it was found that the host material strongly influenced thermal quenching of Ni2+ emission intensity, which had high impact on the value of relative sensitivity (SR). The highest rate of thermal quenching was observed for MgTiO3: Ni2+ nanocrystals with SR>1.4%/K, while in physiological temperature range highest SR was obtained for CaTiO3: Ni2+ (1.4%/K < SR<3.1%/K). Additionally, for two host materials after co-doping with Er3+ ions ratiometric LNTs were accomplished, namely SrTiO3: Ni2+, Er3+ and CaTiO3: Ni2+, Er3+ with the highest obtained SR in physiological temperatures reaching 0.44%/K and 0.37%/K, respectively.

The crucial role of water in the formation of the physiological temperature range for warm-blooded organisms

Abstract We present weighty evidence of specific transformations during thermal motion in bulk water in the physiological temperature range. The vicinity of the temperature point of 315 K (42 °C) is the maximum value for death for many warm-blooded organisms under physiological conditions and at the same time is the upper limit of the temperature range in which the crystal-like behavior of thermal motion in water turns into argon-like (the so-called dynamic phase transition). This temperature is also a threshold point in the temperature dependences of the Zeta potential for the main plasma proteins, such as albumin and fibrinogen, in aqueous solutions. The limitation of the physiological temperature range from the lower temperature limit of 303 K is naturally explained by the clustering of water molecules, which increases strongly with decreasing temperature.

Eu3+−doped titanium oxide nanoparticles for optical thermometry in the first biological window

Lanthanide-based optical nanothermometers, operating in the physiological temperature range (288–323 K), with excitation and emission in the first biological transparent window have special interest for biological applications. In this context, trivalent europium doped titanium oxide (Eu3+:TiO2) nanoparticles were prepared via a sol-gel method and their spectroscopic properties were studied. In order to assess their potential for temperature sensing, excitation and luminescence spectroscopies were performed. We observed that the intensities of the excitation bands for the 7F0→5D0 (576 nm) and 7F2→5D0 (610 nm) transitions, monitoring the 5D0→7F4 (700 nm) transition have a strong dependence on temperature. This dependence, which is explained in terms of a thermal coupling between the Eu3+:7FJ levels, was used for the construction of an optical nanothermometer. Relative sensitivity values between 1.78 and 1.41% K−1, when the temperature of the material increases from 288 to 323 K, were obtained. We show that the nanothermometer calibration can be obtained by a single luminescence room temperature measurement. Our results indicate the potential application of Eu3+:TiO2 nanoparticles for temperature sensing in the first biological window and physiological temperature range.

Synthesis, Cytotoxicity Assessment and Optical Properties Characterization of Colloidal GdPO4:Mn2+, Eu3+ for High Sensitivity Luminescent Nanothermometers Operating in the Physiological Temperature Range.

Herein, a novel synthesis method of colloidal GdPO4:Mn2+,Eu3+ nanoparticles for luminescent nanothermometry is proposed. XRD, TEM, DLS, and zeta potential measurements confirmed the crystallographic purity and reproducible morphology of the obtained nanoparticles. The spectroscopic properties of GdPO4:Mn2+,Eu3+ with different amounts of Mn2+ and Eu3+ were analyzed in a physiological temperature range. It was found that GdPO4:1%Eu3+,10%Mn2+ nanoparticles revealed extraordinary performance for noncontact temperature sensing with relative sensitivity SR = 8.88%/°C at 32 °C. Furthermore, the biocompatibility and safety of GdPO4:15%Mn2+,1%Eu3+ was confirmed by cytotoxicity studies. These results indicated that colloidal GdPO4 doped with Mn2+ and Eu3+ is a very promising candidate as a luminescent nanothermometer for in vitro applications.