State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China.
Anal Chem. 2022 Nov 29;94(47):16345-16352. doi: 10.1021/acs.analchem.2c03290. Epub 2022 Nov 16.
Alzheimer's disease (AD) is a common chronic neurodegenerative disease that manifests as cognitive impairment and behavioral deficits and severely threatens the health of the elderly. Acetylcholinesterase (AChE) plays a vital role in biological signaling and is an essential target for the early diagnosis and treatment of AD. Herein, 2D Zn-TCPP(Fe) nanosheets (NSs) employing Zn and Fe-bound tetrakis(4-carboxyphenyl)porphyrin ligands were prepared through a surfactant-assisted synthetic method. The ultrathin two-dimensional (2D) metal-organic framework structures exhibited high peroxidase-like activity, which allowed the catalysis of the HO-initiated oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB (ox-TMB). Such catalytic performance inspired us to develop a convenient, rapid, and sensitive acetylcholinesterase activity assay, during which AChE can catalyze the substrate acetylthiocholine (ATCh) to produce thiocholine (TCh), and TCh could especially enable the degradation of 2D Zn-TCPP(Fe) NSs accompanied by the reduction of ox-TMB production. Our proposed sensing system exhibited favorable selectivity and sensitivity (LOD of 0.029 mU/mL) and has excellent potential to evaluate AChE activity in human serum samples and to screen AChE inhibitors. This colorimetric assay could provide an alternative pathway for early diagnosis and drug screening of AD, facilitating the development of AD therapy.
阿尔茨海默病（AD）是一种常见的慢性神经退行性疾病，表现为认知障碍和行为缺陷，严重威胁老年人的健康。乙酰胆碱酯酶（AChE）在生物信号中起着至关重要的作用，是 AD 早期诊断和治疗的重要靶点。在此，通过表面活性剂辅助合成方法制备了二维 Zn-TCPP(Fe)纳米片（NSs），其采用 Zn 和 Fe 结合的四（4-羧基苯基）卟啉配体。超薄二维（2D）金属有机骨架结构表现出高过氧化物酶样活性，可催化 HO 引发的无色 3,3',5,5'-四甲基联苯胺（TMB）的氧化，生成蓝色氧化 TMB（ox-TMB）。这种催化性能激发了我们开发一种方便、快速和灵敏的乙酰胆碱酯酶活性测定方法，在该方法中，AChE 可以催化底物乙酰硫代胆碱（ATCh）生成硫代胆碱（TCh），而 TCh 特别能够降解 2D Zn-TCPP(Fe) NSs，同时减少 ox-TMB 的产生。我们提出的传感系统表现出良好的选择性和灵敏度（LOD 为 0.029 mU/mL），并且具有极好的潜力来评估人血清样品中的 AChE 活性和筛选 AChE 抑制剂。这种比色测定法可以为 AD 的早期诊断和药物筛选提供另一种途径，有助于 AD 治疗的发展。
