Bioorthogonal Light-Up Fluorescent Probe Enables Wash-Free Real-Time Dynamic Monitoring of Cellular Glucose Uptake.

As a significant energy source for living systems, the aberrant cellular glucose uptake is seriously implicated in numerous metabolic diseases. Unfortunately, current shortage of robust tools leaves the limitation to understand its precise biology. Herein we presented a bioorthogonal light-up fluorescent probe consist of two reagents, Glu-HT-Me + AzGlu2 , for rapidly responsive (within 25 min), highly specific and sensitive (20-folds enhancement) detection of live-cell glucose uptake based on arylphosphine-induced a-PET effect and Staudinger ligation. Especially, taking the advantage of wash-free characteristic, the probe displayed the real-time dynamic monitoring of cellular glucose uptake. Furthermore, it was successfully capable of not only differentiating cancer cells from normal cells, but also allowing evaluation of anticancer/glycolysis/transport mediated glucose flux. Importantly, it was employed to monitor the fluctuations of glucose uptake in a doxycycline-inducible K-ras G12 V expression oncogenic cell system, implying its potential as a valuable tool to explore glucose uptake biology.