Current and Future of “Turn‐On” Based Small‐Molecule Copper Probes for Cuproptosis

Abstract

Increasing evidence shows that abnormal copper (Cu) metabolism is highly related to many diseases, such as Alzheimer's disease, Wilson's disease, hematological malignancies and Menkes disease. Very recently, cuproptosis, a Cu‐dependent, programmed cell death was firstly described by Tsvetkov et al. in 2022. Their findings may provide a new perspective for the treatment of related diseases. However, the concrete mechanisms of these diseases, especially cuproptosis, remain completely unclear, the reason of which may be a lack of reliable tools to conduct highly selective, sensitive and high‐resolution imaging of Cu in complex life systems. So far, numerous small‐molecular fluorescent probes have been designed and utilized to explore the Cu signal pathway. Among them, fluorescence turn‐on probes greatly enhance the resolution and accuracy of imaging and may be a promising tool for research of investigation into cuproptosis. This review summarizes the probes developed in the past decade which have the potential to study cuproptosis, focusing on the design strategies, luminescence mechanism and biological‐imaging applications. Besides, we put forward some ideas concerning the design of next‐generation probes for cuproptosis, aiming to tackle the main problems in this new field. Furthermore, the prospect of cuproptosis in the treatment of corresponding diseases is also highlighted.

Antitumor Activity and Mechanistic Insights of a Mitochondria-Targeting Cu(I) Complex

“…Another pivotal issue for further understanding the mechanism of cuproptosis is the distinguishing visualization or quantitation of intracellular Cu­(I) and Cu­(II). Fluorescent probes have been developed for tracing intracellular copper ions, and thus are considered as a reliable tool to sensitively and selectively determine Cu­(I) and Cu­(II) separately . Thus, CBP exhibits antitumor effects through a complex mechanism that requires further investigations.…”