Employing an ICT-FRET Integration Platform for the Real-Time Tracking of SO_2 Metabolism in Cancer Cells and Tumor Models

摘要

Glutathione (GSH) mediates a wide variety of biological events and human diseases. Although it has been the subject of intense study in recent years, a further understanding of its molecular mechanisms and metabolism routes in living cells has remained limited due to a lack of appropriate analytical tools. Sulfur dioxide (SO_2), an important metabolite of GSH, is usually associated with the symptoms of neurological disorders, cardiovascular diseases, and lung cancer. Herein, a novel multisignal fluorescent probe was rationally designed and exploited for the simultaneous detection of GSH and its metabolite SO_2 via an ICT-FRET synergetic mechanism. The probe shows completely reversed fluorescence responses toward GSH (enhanced red emission) and SO_2 (annihilated red fluorescence) with high selectivity and sensitivity. In particular, the probe displayed completely different fluorescent signals (blue-shift) with SO_2 in the presence of GSH, thereby allowing the imaging of the metabolism process of GSH to SO_2 in two independent channels without spectral cross interference. Given these advantages, this probe has been successfully applied to the real-time monitoring of the SO_2 metabolic process in living cells and mice models, and it has thus been found that GSH can metabolize SO_2 by enzymatic reaction with TST (thiosulfate sulphurtransferase); additionally, SO_2 was transformed into sulfate under SUOX (sulfite oxidase). We anticipate that this research will provide a convenient and efficient tool for understanding the interrelated physiological functions of GSH and SO_2 in more biosystems.