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 conformation...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 immunoaf-finity not only fully exposed the binding sites of AChE on the cell membrane but also ensured its confor-mation 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 exhib-ited a satisfactory sensitivity(limit of detection�0.41 pmol/L).Ultimately,six potentially active com-pounds against AD(baicalin,geniposide,gastrodin,berberine,rhynchophylline,and senkyunolide A)were rapidly identified and evaluated from TCMs.This project provides a promising strategy for devel-oping cell membrane-coated electrochemical biosensors.The application of cell membrane-coated elec-trochemical biosensors with well-defined cell membrane orientation further expands new perspectives and methods for AChE-targeted anti-AD research.展开更多
基金the National Natural Science Foun-dation of China(Nos.82104125 and 82373832)China Post-doctoral Science Foundation(No.2021M702632)Key Research and Development Projects of Shaanxi Province(Nos.2023-YBSF-145,2024SF-YBXM-469,2024JC-YBMS-651).
文摘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 immunoaf-finity not only fully exposed the binding sites of AChE on the cell membrane but also ensured its confor-mation 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 exhib-ited a satisfactory sensitivity(limit of detection�0.41 pmol/L).Ultimately,six potentially active com-pounds against AD(baicalin,geniposide,gastrodin,berberine,rhynchophylline,and senkyunolide A)were rapidly identified and evaluated from TCMs.This project provides a promising strategy for devel-oping cell membrane-coated electrochemical biosensors.The application of cell membrane-coated elec-trochemical biosensors with well-defined cell membrane orientation further expands new perspectives and methods for AChE-targeted anti-AD research.
