Fabricationof a Redox-Reversible Near-Infrared FluorogenicProbe for Ferroptosis Process Monitoring and the Early Diagnosis ofDiabetes

Ferroptosis is a type of cell death triggered by the iron-dependent accumulation of lipid peroxides in cells. Diabetes, a chronic metabolic disorder characterized by hyperglycemia, can lead to various health complications. The process of ferroptosis and the progression of diabetes are closely linked to redox homeostasis, which is regulated by the levels of reactive oxygen and sulfur species. Currently, there are no fluorescent probes available to monitor changes in redox homeostasis during ferroptosis and diabetes. Here, we report the first endeavor to create a reversible near-infrared fluorogenic (NIRF) probe for monitoring the process of ferroptosis reversal and precise diabetes diagnosis. In vitro data demonstrated that NIR-CSTe could cyclically and reversibly detect ONOO^– and GSH up to four times with minimal loss in fluorescence intensity. With the help of NIR-CSTe, we observed that HT-1080 cells, induced to undergo ferroptosis by erastin after being washed with PBS for 24 h and then treated with ferrostatin-1, showed a recovery in intracellular GSH levels. In contrast, treatment with deferoxamine did not yield similar results. Lastly, NIR-CSTe was also utilized for the early diagnosis and efficacy assessment of diabetes in relation to ONOO^–/GSH redox balance, with results illustrating that the combined administration of metformin and empagliflozin was more effective than using either drug alone. Thus, this smart probe holds significant potential as an essential tool for clinical diagnosis and treatment of diseases associated with redox homeostasis.