Recent advances and future perspectives of fluorescent probes for serine hydrolases

Serine hydrolases (SHs) are a family of enzymes characterized by a catalytic triad consisting of serine, histidine, and aspartate. Alterations in their in vivo activity are closely linked to the development and progression of various diseases, including metabolic disorders, neurological diseases, inflammatory and immune-related conditions, and cancer. Therefore, the development of novel bioanalytical methods capable of monitoring dynamic changes in SH activity within living systems is of significant importance for both disease diagnosis and therapeutic evaluation. In recent years, responsive probes for fluorescence analysis of SHs have advanced rapidly; however, a comprehensive and systematic review summarizing these probes is still lacking. This article overviews recent research advances in the development of fluorescent probes for SHs detection, focusing on key SH subfamilies, including serine esterases (e.g., acetylcholinesterase, butyrylcholinesterase, carboxylesterases, and lipases), serine proteases (e.g., chymotrypsin, neutrophil elastase, and trypsin), and serine carboxypeptidases. It discusses the chemical structures and the response mechanisms of the probes, as well as their emerging biomedical applications. This review also highlights several current challenges in the development of fluorescent probes for SHs and discusses future research directions, with the aim of elucidating the pathophysiological significance of SHs and promoting their broader applications in biomedical diagnostics and translational research.