AUTHOR=Qin Xue , Zhang Shuping , Guo Xiaolu , Liu Xingyue , Shen Xing-Can 

TITLE=A cascading-response fluorescent probe for real-time pH monitoring during cysteine-depletion process in pancreatic cancer cells

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2022.1062781

DOI=10.3389/fbioe.2022.1062781

ISSN=2296-4185

ABSTRACT=Pancreatic cancer (PC) is one of the deadliest human malignancies and exploring the complex molecular mechanism behind cell death will greatly promote the clinical treatment of PC. Here, we report a cascading-response fluorescent imaging probe, Cy-Cys-pH, for the sequential detection of cysteine (Cys) and pH in pancreatic cancer cells. In the presence of Cys, Cys-mediated cleavage of acrylate group makes Cy-Cys-pH to be transformed into Cy-Cys-O, which induces intense fluorescence enhancement at 725 nm. Then, Cy-Cys-O is protonated to obtain Cy-Cys-OH and the fluorescence emission shifted to 682 nm showing ratiometric pH response. Furthermore, using Cy-Cys-pH, we monitored the intracellular pH during the therapeutic process with anticancer drugs and evaluated the ability of three anticancer drugs to kill Panc-1 cells, demonstrating that associating Cys and pH is in part an effective anticancer strategy in the treatment of pancreatic cancer. Significantly, Cy-Cys-pH is able to real-time monitor and image pH changes during Cys depletion which further revealing the molecular mechanism of Cys-depleted pancreatic cancer cell death providing a powerful molecular tool for the precise treatment of PC.