Ultrasensitive Small-Molecule Fluorescent Thermometer Reveals Hot Mitochondria in Surgically Resected Human Tumors

Abstract

The Warburg effect suggests that upregulated glycolysis arising from high glucose uptake in cancer cells might be accompanied with suppressed mitochondrial respiration. However, recent studies have shown that the mitochondrial temperature in cancer cells could be relatively higher than that in normal cells, suggesting hyperactive mitochondrial respiration in cancer cells. However, hot mitochondria have not been reported in patients with cancer. Here, near-infrared small-molecule fluorescent probes TRNs are rationally designed with two ethyl amino groups as the temperature-sensitive moiety. Afterward, a mitochondrial targeting group is installed via ether bonds on TRN-8 to build MTN. To the best of our knowledge, MTN is the near-infrared probe with the highest sensitivity for mitochondrial temperature. Moreover, it also displays high photostability, wide linearity, and high specificity. Using MTN, we can monitor the ups and downs of mitochondrial temperature in cancer cells upon the perturbations of mitochondrial respiration. Furthermore, we demonstrate that the mitochondrial temperature in surgically resected human tumors is relatively higher than that in paracancerous tissues. Our results indicate that relatively hot mitochondria may exist in tumors from patients. We envisage that our study provides critical evidence for revisiting the Warburg effect and cancer metabolism.

Response strategies and biological applications of organic fluorescent thermometry: cell- and mitochondrion-level detection

“…8). 80 The probe demonstrated high sensitivity and NIR emission (600–670 nm). The fluorescence intensity at 660 nm was increased by approximately 28-fold as the temperature decreased from 60 °C to 25 °C (Fig.…”

Organic Fluorescent Probes for Monitoring Micro-Environments in Living Cells and Tissues

“…Mitochondrial temperature plays a vital role in cells and tissues, and recent studies suggest that cancer cells have relatively hot mitochondria, which indicates that the active respire of mitochondria in cancer cells [10,113]. Chang et al have reported a small molecule mitochondria-targeted fluorescent probe (Mito 22 hermos yellow) with rosamine structure for monitoring temperature changes in mitochondria [114].…”

“…The physiological process, such as enzyme-based catalysis and 2 of 30 lipid composition, is closely associated with polarity [8,9]. Finally, various physiological and pathological states are in company with the variation of temperatures, so the temperature could reflect the state of cells and tissues [10,11]. Conspicuously, the microenvironment is of vital importance to biological organisms.…”

A novel fluorescence probe for simultaneous detection of mitochondrial viscosity in hepatic ischemia reperfusion injury models

“…Currently, uorescent imaging has garnered notable interest owing to its capability for relatively straightforward operation, high sensitivity, and real-time visualization. [18][19][20][21] Therefore, the detection of intracellular viscosity with the aid of a uorescence spectrometer may become a new-established method, potentially being used for HIRI early diagnosis. To date, considerable and outstanding results have been achieved in imaging viscosity alteration in vivo.…”