AChE-activatable turn-on fluorescent probes for real-time monitoring of drug release in Parkinson's disease models

Jing Wang; Yu Zeng; Ran Ji; Ling Li; Zhigang Sun; Tony D. James; Xiangjie Luo; Yong Qian

doi:10.1016/j.microc.2026.119544

AChE-activatable turn-on fluorescent probes for real-time monitoring of drug release in Parkinson's disease models

Jing Wang
, Yu Zeng
, Ran Ji
, Ling Li
, Zhigang Sun
, Tony D. James
, Xiangjie Luo
, Yong Qian

Nanjing Normal University
Linyi Central Hospital
Henan Normal University

Research output: Contribution to journal › Article › peer-review

20 Downloads (Pure)

Abstract

The detection of disease-associated enzymatic biomarkers for targeted drug release and real-time imaging remains a critical challenge in Parkinson's disease (PD) therapy. Herein, we rationally designed a series of AChE-triggered fluorescent probes (ZGT-1, ZGT-2, and ZGT-3) incorporating disulfiram (DSF) as a model cargo. Among them, ZGT-3 exhibits an excellent AChE-selective fluorescence turn-on response under physiological conditions, with negligible interference from other enzymes. In living SH-SY5Y cells, ZGT-3 visualizes AChE upregulation under H₂O₂-induced oxidative stress and MPP⁺-induced neurotoxicity, and its fluorescence is effectively suppressed by the AChE inhibitor neostigmine, confirming on-site activation. By integrating real-time fluorescence monitoring with AChE-triggered drug release functionality, ZGT-3 provides a reliable analytical platform for investigating prodrug activation mechanisms in neuroinflammatory conditions.

Original language	English
Article number	119544
Number of pages	8
Journal	Microchemical Journal
Volume	229
Early online date	27 Aug 2026
DOIs	https://doi.org/10.1016/j.microc.2026.119544
Publication status	E-pub ahead of print - 27 Aug 2026

Data Availability Statement

Data will be made available on request.

Funding

The authors acknowledge research support from the National Natural Science Foundation of China (22477061, 22507057) and the Natural Science Foundation of Jiangsu Province (BK20240580). T. D. J. wishes to thank the University of Bath and the Open Research Fund of the School of Chemistry and Chemical Engineering, Henan Normal University (2020ZD01) for support.

Keywords

Acetylcholinesterase
Drug release monitoring
Fluorescent probe
Parkinson's disease

ASJC Scopus subject areas

Analytical Chemistry
Spectroscopy

Access to Document

10.1016/j.microc.2026.119544

Manuscript-160926
This the Author Accepted Manuscript of published paper located at 10.1016/j.microc.2026.119544
Accepted author manuscript, 821 KBLicence: CC BY

Cite this

@article{9581b616b90740c9b769d901b577d421,

title = "AChE-activatable turn-on fluorescent probes for real-time monitoring of drug release in Parkinson's disease models",

abstract = "The detection of disease-associated enzymatic biomarkers for targeted drug release and real-time imaging remains a critical challenge in Parkinson's disease (PD) therapy. Herein, we rationally designed a series of AChE-triggered fluorescent probes (ZGT-1, ZGT-2, and ZGT-3) incorporating disulfiram (DSF) as a model cargo. Among them, ZGT-3 exhibits an excellent AChE-selective fluorescence turn-on response under physiological conditions, with negligible interference from other enzymes. In living SH-SY5Y cells, ZGT-3 visualizes AChE upregulation under H2O2-induced oxidative stress and MPP+-induced neurotoxicity, and its fluorescence is effectively suppressed by the AChE inhibitor neostigmine, confirming on-site activation. By integrating real-time fluorescence monitoring with AChE-triggered drug release functionality, ZGT-3 provides a reliable analytical platform for investigating prodrug activation mechanisms in neuroinflammatory conditions.",

keywords = "Acetylcholinesterase, Drug release monitoring, Fluorescent probe, Parkinson's disease",

author = "Jing Wang and Yu Zeng and Ran Ji and Ling Li and Zhigang Sun and James, \{Tony D.\} and Xiangjie Luo and Yong Qian",

year = "2026",

month = aug,

day = "27",

doi = "10.1016/j.microc.2026.119544",

language = "English",

volume = "229",

journal = "Microchemical Journal",

issn = "0026-265X",

publisher = "Elsevier",

}

TY - JOUR

T1 - AChE-activatable turn-on fluorescent probes for real-time monitoring of drug release in Parkinson's disease models

AU - Wang, Jing

AU - Zeng, Yu

AU - Ji, Ran

AU - Li, Ling

AU - Sun, Zhigang

AU - James, Tony D.

AU - Luo, Xiangjie

AU - Qian, Yong

PY - 2026/8/27

Y1 - 2026/8/27

N2 - The detection of disease-associated enzymatic biomarkers for targeted drug release and real-time imaging remains a critical challenge in Parkinson's disease (PD) therapy. Herein, we rationally designed a series of AChE-triggered fluorescent probes (ZGT-1, ZGT-2, and ZGT-3) incorporating disulfiram (DSF) as a model cargo. Among them, ZGT-3 exhibits an excellent AChE-selective fluorescence turn-on response under physiological conditions, with negligible interference from other enzymes. In living SH-SY5Y cells, ZGT-3 visualizes AChE upregulation under H2O2-induced oxidative stress and MPP+-induced neurotoxicity, and its fluorescence is effectively suppressed by the AChE inhibitor neostigmine, confirming on-site activation. By integrating real-time fluorescence monitoring with AChE-triggered drug release functionality, ZGT-3 provides a reliable analytical platform for investigating prodrug activation mechanisms in neuroinflammatory conditions.

AB - The detection of disease-associated enzymatic biomarkers for targeted drug release and real-time imaging remains a critical challenge in Parkinson's disease (PD) therapy. Herein, we rationally designed a series of AChE-triggered fluorescent probes (ZGT-1, ZGT-2, and ZGT-3) incorporating disulfiram (DSF) as a model cargo. Among them, ZGT-3 exhibits an excellent AChE-selective fluorescence turn-on response under physiological conditions, with negligible interference from other enzymes. In living SH-SY5Y cells, ZGT-3 visualizes AChE upregulation under H2O2-induced oxidative stress and MPP+-induced neurotoxicity, and its fluorescence is effectively suppressed by the AChE inhibitor neostigmine, confirming on-site activation. By integrating real-time fluorescence monitoring with AChE-triggered drug release functionality, ZGT-3 provides a reliable analytical platform for investigating prodrug activation mechanisms in neuroinflammatory conditions.

KW - Acetylcholinesterase

KW - Drug release monitoring

KW - Fluorescent probe

KW - Parkinson's disease

UR - https://www.scopus.com/pages/publications/105048573924

U2 - 10.1016/j.microc.2026.119544

DO - 10.1016/j.microc.2026.119544

M3 - Article

AN - SCOPUS:105048573924

SN - 0026-265X

VL - 229

JO - Microchemical Journal

JF - Microchemical Journal

M1 - 119544

ER -

AChE-activatable turn-on fluorescent probes for real-time monitoring of drug release in Parkinson's disease models

Abstract

Data Availability Statement

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this