Engineering of a low intrinsic fluorescence and chemical-stable fluorescent probe enables highly sensitive detection of biothiols and high-fidelity imaging of dihydroartemisinin-induced ferroptosis

Abstract

Ferroptosis modulation represents a novel therapeutic strategy for pancreatic ductal adenocarcinoma (PDAC), where precise control of ferroptotic levels is imperative for optimizing treatment efficacy. Dihydroartemisinin (DHA) has emerged as a promising candidate in PDAC therapy, potentially through its ability to induce ferroptosis and thereby enhance the synergistic effects of PDAC treatments. However, the mechanism study of DHA-induced ferroptosis is limited by the lack of accredited biomarkers and the absence of powerful fluorescent probe with good stability towards reactive oxygen species (ROS) and low intrinsic fluorescence, which is necessary for high-fidelity and sensitive monitoring ferroptosis in PDAC. In this innovative study, we engineered a novel fluorescent probe (BOD-NBD), characterized by minimal intrinsic fluorescence and exceptional stability against ROS, enabling highly sensitive and accurate detection and imaging of biothiols in PDAC. The probe achieved high signal-to-back ratio, high sensitivity and high specificity response to biothiols. Using this probe, significant depletion of biothiols in PDAC cells during ferroptosis was observed. The probe was further successfully applied for monitoring DHA-induced ferroptosis in Panc02 cells with reliable imaging results. Moreover, for the first time, we observed an interesting experimental finding that joint use of erastin and DHA or cisplatin and DHA could exacerbate the consumption of biothiols, which may imply an aggravation of ferroptosis in PDAC, demonstrating great significance in the development of novel therapeutic schedule for the treatment of PDAC.