L-cysteine derived Golgi apparatus-targeting carbon dots for visualizing glutathione fluctuations during ferroptosis

Ferroptosis is a form of cell death induced by iron accumulation of lipid peroxides. The Golgi apparatus maintains intracellular redox homeostasis during ferroptosis by regulating glutathione (GSH). Therefore, real-time monitoring of GSH levels on the Golgi apparatus is essential to comprehend its function in the progress of ferroptosis and investigate the mechanisms of ferroptosis-mediated diseases. Herein, we synthesized carbon dots, L-Cys-CDs, with excellent photostability under a low-temperature oil bath at 80 °C employing L-cysteine as carbon source. L-Cys-CDs exhibited fast response and excellent selectivity to GSH. The investigations on the targeting mechanism indicated that the L-type stereo-structure and free sulfhydryl groups synergistically resulted in the ability of L-Cys-CDs to target the Golgi apparatus specifically. Due to the overexpression of GSH in cancer cells, L-Cys-CDs allowed differentiation of normal cells and cancer cells. More importantly, L-Cys-CDs could be applied to monitor the reduction of GSH during ferroptosis in cells and zebrafish, and its reversal by ferroptosis inhibitors. In light of these properties, L-Cys-CDs will provide an opportunity for a more in-depth insight into the role of GSH in ferroptosis, which is important for research into the pathological pathway and therapeutic choice for ferroptosis-related diseases.