Electrochemical biosensors with right-side-out-oriented cell membrane coating for the evaluation of AChE inhibitors as potential anti-Alzheimer's disease agents.
10.1016/j.apsb.2025.09.032
- Author:
Ying ZHAO
1
;
Xia LIU
1
;
Shuning YANG
1
;
Jiabo WANG
1
;
Dan WU
1
;
Yusi BU
1
;
Xiaoyu XIE
1
Author Information
1. School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
- Publication Type:Journal Article
- Keywords:
Acetylcholinesterase inhibitors;
Alzheimer's disease;
Drug evaluation;
Electrochemical biosensors;
Immunological affinity;
Red blood cell membranes;
Right-side-out-oriented cell membrane coating;
Traditional Chinese medicines
- From:
Acta Pharmaceutica Sinica B
2025;15(11):5988-6000
- CountryChina
- Language:English
-
Abstract:
Biosensors based on acetylcholinesterase (AChE) are crucial for early diagnosis, less invasive treatment, and drug evaluation of Alzheimer's disease (AD). However, existing technologies often suffer from enzyme conformational changes, leading to altered activity and loss and reduced sensor efficacy. To address this challenge, we developed a novel right-side-out-oriented red blood cell membrane-coated electrochemical biosensors (ROCMCBs) to evaluate AChE inhibitors from traditional Chinese medicines (TCMs) as potential anti-AD agents. The developed right-side-out-oriented coating based on immunoaffinity not only fully exposed the binding sites of AChE on the cell membrane but also ensured its conformation and stability as a peripheral membrane-anchoring protein, which was conducive to maintaining its biological activity and producing optimal interaction with drugs. At the same time, the biosensors exhibited a satisfactory sensitivity (limit of detection = 0.41 pmol/L). Ultimately, six potentially active compounds against AD (baicalin, geniposide, gastrodin, berberine, rhynchophylline, and senkyunolide A) were rapidly identified and evaluated from TCMs. This project provides a promising strategy for developing cell membrane-coated electrochemical biosensors. The application of cell membrane-coated electrochemical biosensors with well-defined cell membrane orientation further expands new perspectives and methods for AChE-targeted anti-AD research.
