Er‐Based Luminescent Nanothermometer to Explore the Real‐Time Temperature of Cells under External Stimuli

Abstract

Intracellular temperature varies as changes in cellular activities including enzyme reactions, [2] cell division, [3] gene expression, [4] and cell-selective treatment to the disease. [5] Studies have shown that cells could respond to regulate intracellular temperature, [6] for instance, mitochondrial heat generation of brown fat cells, heat shock protein production [7] to prevent the necrosis and apoptosis of certain cells, and heat emission at tumor metabolism or local infection according to medical science. [8] However, how would cellular temperature changes due to external thermal stimulation, and the variance between different species of cells, remain unknown. Thus, the measurement of real-time intracellular temperature under stimuli is of great importance for studying cellular processes and optimizing photothermal therapy. [9] This detection helps to explore and discover new phenomena and laws, meanwhile it is necessary to ensure the accuracy of detection. [10] Therefore, the real-time and accurate temperature probe in cells is still urgently needed. For that, research on intracellular thermometers has developed rapidly in the past decade, including nanomaterials based on luminescence are studied widely. [11] Besides a few reports of intrusive thermometers, noncontact luminescence thermometry is mainly used in vivo and in vitro, including infrared thermal detectors, small molecular compounds, fluorescent proteins, quantum dots, upconversion nanoparticles (UCNPs), etc. [12] Rare earth luminescent materials have been widely used because of their prominent advantages such as narrow emission band, good light stability, long luminescent lifetime, and decrease the interference of the autofluorescence from biological tissue. [13] After properly doping, rare earth luminescent nanomaterials have superior properties of temperature response with high resolution and sensitivity of optical signals, and their determination is relatively toilless. [14] Among them, Er 3+ doping nanomaterial is a very preeminent thermometer based on the change of the ratio of two emissions determined by Boltzmann distribution law, which is theoretically independent of the external factors. [15] It provides a chance to achieve the high accuracy of detection and imaging, and the obvious green visible light of Er 3+ is suitable for cellular measurement without tissue covered. However, there are significant disadvantages for this type of probe in biological measurement:Temperature as a typical parameter, which influences the status of living creatures, is essential to life activities and indicates the initial cellular activities. In recent years, the rapid development of nanotechnology provides a new tool for studying temperature variation at the micro-or nano-scales. In this study, an important phenomenon is observed at the cell level using luminescent probes to explore intracellular temperature changes, based on Yb-Er doping nanoparticles with special upconversion readout mode and intensity ratio signals (I 525 and I 545 ). Further optimiza...

A Lanthanide Upconversion Nanothermometer for Precise Temperature Mapping on Immune Cell Membrane

“…After eliminating the unreacted excess dyes by centrifugation, fluorescence spectra of samples showed the typical emission band of dye centered at ∼700 nm, indicative of the potent click chemistry conjugation ability of NPs-DBCO (Figure S10). More importantly, NPs-DBCO showed good thermal sensing capability in the range from 20 to 80 °C with a relative sensing sensitivity of 1.4% K –1 at 37 °C (Figure f), which is comparable to that of the reported nanothermometers …”

“…More importantly, NPs-DBCO showed good thermal sensing capability in the range from 20 to 80 °C with a relative sensing sensitivity of 1.4% K −1 at 37 °C (Figure 2f), which is comparable to that of the reported nanothermometers. 25 We next investigated the cell membrane labeling capability of NPs-DBCO in living cells by confocal fluorescence imaging. This experiment was studied on Jurkat T cells, which is a generally used T lymphocyte cell model for exploring the temperature-sensitive immune response signaling.…”

“…Luminescent nanothermometry has attracted much attention in the past decade for temperature imaging in living cells and in vivo, which is established based on luminescent nanoparticles (NPs), such as quantum dots, − lanthanide-doped NPs, − polymeric NPs, − metal nanocrystals, and nanodiamonds . Notably, lanthanide-doped upconversion NPs (UCNPs) feature tunable and narrow emissions, high photostability, and low cytotoxicity, exhibiting unique advantages in the sensing of temperature. − Advances in the design of UCNPs have enabled noninvasive monitoring of the dynamic thermogenesis and heat distribution in individual cells and the temperature change during hyperthermia and photodynamic therapy in vivo. − In addition, UCNPs confer in vivo sensitive temperature imaging in the disease progression (e.g., inflammation). , Recently, the sensitive membrane thermometry of single adherent cell has been reported based on UCNPs-decorated spider silks .…”

Near-infrared light triggered in situ release of CO for enhanced therapy of glioblastoma

“…Taking the advantages of NIR excitation and multicolor emission of UCNPs, the penetration depth of excitation light is enhanced and meanwhile simultaneous Scheme 1 Schematic illustration of the synthesis process of lanthanide-doped nanoparticles loaded with photosesitizer Ce6 (chlorin e6) and photoCORM 3HBQ encapsulated by brain tumor cell membranes (UCNPs@Ce6/3HBQ@CM) and the anti-glioma mechanism (OA and PC represent oleic acid and phosphatidylcholine, respectively) generation of CO and ROS in tumor site can be achieved. Besides, efficient upconversion luminescence under NIR excitation can be utilized to track the therapeutic platform in vivo [29][30][31][32][33][34][35]. As far as we know, this is the first GBM therapy platform in which both PDT and CO release is simultaneously triggered by NIR light.…”

Facile synthesis of rare earth-doped CeF3 two-dimensional nanosheets and their application in ratiometric luminescence temperature sensing

“…Due to the high sensitivity, fast response, inertness to strong electrical fields and non-contact measurement, fluorescence-based temperature sensors have attracted great interest. [37][38][39][40][41][42] Among them, temperature sensors based on the fluorescence intensity ratio technology do not require additional calibration of the emission intensity, which has obvious advantages because it can reduce the influence of external conditions during the temperature measurement process, thereby improving the resolution and accuracy. 43,44 In the past decades, many kinds of luminescent materials, such as organic molecules and quantum dots, have been tested for temperature sensing.…”