Monitoring acetylcholinesterase level changes under oxidative stress through ESIPT-ICT-based near-infrared fluorescent probe

Oxidative stress plays an important role in pathology, and contributes to a variety of diseases, including inflammation, neurodegenerative diseases, and cancer. Research studies have shown that acetylcholinesterase (AChE) plays a key role in regulating oxidative stress. However, an effective analytical method for real-time monitoring of AChE under oxidative stress is still lacking. Currently, fluorescent probes based on dual sensing mechanisms have attracted great attention by combining and amplifying the advantages of both mechanisms. In this work, two NIR fluorescent probes (SNCN-AE and SNC-AE) that combined ESIPT and ICT processes were designed and synthesized for accurate detection of AChE activity. After the probes reacted with AChE, the strong electron push-pull effect enhanced the ICT process, which further synergized with the ESIPT effect, resulting in a distinct NIR fluorescence signal accompanied by a large Stokes shift. In particular, SNCN-AE showed better detection performance of fast response, good photostability and low cytotoxicity, which was highly suitable for imaging of endogenous AChE in living system. Importantly, SNCN-AE had been successfully applied for moni-toring AChE under oxidative stress in PC12 cells and zebrafish model. These excellent properties made probes the promising tools for studying oxidative stress and related diseases.

Automated summary

Oxidative stress plays a significant role in various diseases, and acetylcholinesterase (AChE) plays a key role in regulating oxidative stress. However, there is a lack of effective analytical method for real-time monitoring of AChE under oxidative stress. This study designed and synthesized two NIR fluorescent probes (SNCN-AE and SNC-AE) for accurate detection of AChE activity by combining ESIPT and ICT processes. These probes showed distinct NIR fluorescence signals and large Stokes shifts, and SNCN-AE exhibited better detection performance and low cytotoxicity, making it suitable for imaging endogenous AChE in living systems. Importantly, SNCN-AE was successfully applied for monitoring AChE under oxidative stress in PC12 cells and zebrafish model, making it a promising tool for studying oxidative stress and related diseases.