Accurate HER2 determination in breast cancer: a prominent COF-immobilized enzyme-enhanced electrochemical aptasensor employing 4-acetamidophenol as an efficient mediator

Abstract An effective strategy for enzyme-enhanced electrochemical detection of human epidermal growth factor receptor 2 (HER2) is proposed for breast cancer diagnosis. This strategy utilizes a three-dimensional mesoporous covalent organic framework (COF), immobilized horseradish peroxidase (HRP), a...

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Main Authors: Yue Zhang, Shuyi Chen, Jie Ma, Xiaobin Zhou, Xinchen Sun, Chenglin Zhou
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Journal of Nanobiotechnology
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Online Access:https://doi.org/10.1186/s12951-024-03035-w
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author Yue Zhang
Shuyi Chen
Jie Ma
Xiaobin Zhou
Xinchen Sun
Chenglin Zhou
author_facet Yue Zhang
Shuyi Chen
Jie Ma
Xiaobin Zhou
Xinchen Sun
Chenglin Zhou
author_sort Yue Zhang
collection DOAJ
description Abstract An effective strategy for enzyme-enhanced electrochemical detection of human epidermal growth factor receptor 2 (HER2) is proposed for breast cancer diagnosis. This strategy utilizes a three-dimensional mesoporous covalent organic framework (COF), immobilized horseradish peroxidase (HRP), and a novel redox mediator, 4-acetamidophenol (APAP). The mesoporous structure, with encapsulation effect, and good biocompatibility of COF, makes the functionalized COF an efficient carrier for HRP immobilization (HRP-Ab-AuNPs@COF). It demonstrates superior catalytic activity, stability, and electrochemical performance compared to free HRP, thus making it an ideal probe for simultaneous target recognition and signal amplification. APAP is screened from four candidate phenolic compounds based on its high formal potential (0.32 V vs. Ag/AgCl), rapid electron transfer activity (kapp = 2.80 × 105 M− 1 s− 1), excellent solubility and stability. These properties prove significantly better than the conventional mediator hydroquinone (HQ), achieving a higher signal-to-background ratio. By integrating decorated multi-walled carbon nanotubes as substrate materials, the electrochemical aptasensor achieves a low HER2 detection limit (0.418 pg mL− 1) with high specificity. This method’s selectivity surpasses that of the HQ-mediated method by 59–73%. Moreover, the aptasensor can effectively distinguish breast cancer patients and healthy individuals, as well as patients at different stages of the disease with high accuracy (AUC = 0.928). This performance exceeds traditional biomarkers CEA and CA15-3. This work paves novel avenues for innovative applications of COF-immobilized enzymes and the novel mediator APAP in electrochemical biosensing, thus holding significant promise for individualized breast cancer diagnosis and treatment.
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spelling doaj-art-50b45f7277004ee4be5ff8dbe1e7c0e22024-12-01T12:43:06ZengBMCJournal of Nanobiotechnology1477-31552024-11-0122111510.1186/s12951-024-03035-wAccurate HER2 determination in breast cancer: a prominent COF-immobilized enzyme-enhanced electrochemical aptasensor employing 4-acetamidophenol as an efficient mediatorYue Zhang0Shuyi Chen1Jie Ma2Xiaobin Zhou3Xinchen Sun4Chenglin Zhou5Clinical Medical Laboratory Center, Gaogang Branch, Taizhou School of Clinical Medicine, Nanjing Medical University, The Affiliated Taizhou People’s Hospital of Nanjing Medical UniversityClinical Medical Laboratory Center, Gaogang Branch, Taizhou School of Clinical Medicine, Nanjing Medical University, The Affiliated Taizhou People’s Hospital of Nanjing Medical UniversityClinical Laboratory Department, The Second Affiliated Hospital of Anhui Medical UniversityClinical Medical Laboratory Center, Gaogang Branch, Taizhou School of Clinical Medicine, Nanjing Medical University, The Affiliated Taizhou People’s Hospital of Nanjing Medical UniversityClinical Medical Laboratory Center, Gaogang Branch, Taizhou School of Clinical Medicine, Nanjing Medical University, The Affiliated Taizhou People’s Hospital of Nanjing Medical UniversityClinical Medical Laboratory Center, Gaogang Branch, Taizhou School of Clinical Medicine, Nanjing Medical University, The Affiliated Taizhou People’s Hospital of Nanjing Medical UniversityAbstract An effective strategy for enzyme-enhanced electrochemical detection of human epidermal growth factor receptor 2 (HER2) is proposed for breast cancer diagnosis. This strategy utilizes a three-dimensional mesoporous covalent organic framework (COF), immobilized horseradish peroxidase (HRP), and a novel redox mediator, 4-acetamidophenol (APAP). The mesoporous structure, with encapsulation effect, and good biocompatibility of COF, makes the functionalized COF an efficient carrier for HRP immobilization (HRP-Ab-AuNPs@COF). It demonstrates superior catalytic activity, stability, and electrochemical performance compared to free HRP, thus making it an ideal probe for simultaneous target recognition and signal amplification. APAP is screened from four candidate phenolic compounds based on its high formal potential (0.32 V vs. Ag/AgCl), rapid electron transfer activity (kapp = 2.80 × 105 M− 1 s− 1), excellent solubility and stability. These properties prove significantly better than the conventional mediator hydroquinone (HQ), achieving a higher signal-to-background ratio. By integrating decorated multi-walled carbon nanotubes as substrate materials, the electrochemical aptasensor achieves a low HER2 detection limit (0.418 pg mL− 1) with high specificity. This method’s selectivity surpasses that of the HQ-mediated method by 59–73%. Moreover, the aptasensor can effectively distinguish breast cancer patients and healthy individuals, as well as patients at different stages of the disease with high accuracy (AUC = 0.928). This performance exceeds traditional biomarkers CEA and CA15-3. This work paves novel avenues for innovative applications of COF-immobilized enzymes and the novel mediator APAP in electrochemical biosensing, thus holding significant promise for individualized breast cancer diagnosis and treatment.https://doi.org/10.1186/s12951-024-03035-wCovalent organic frameworkImmobilized enzymeElectrochemical aptasensing4-acetamidophenolBreast cancer
spellingShingle Yue Zhang
Shuyi Chen
Jie Ma
Xiaobin Zhou
Xinchen Sun
Chenglin Zhou
Accurate HER2 determination in breast cancer: a prominent COF-immobilized enzyme-enhanced electrochemical aptasensor employing 4-acetamidophenol as an efficient mediator
Journal of Nanobiotechnology
Covalent organic framework
Immobilized enzyme
Electrochemical aptasensing
4-acetamidophenol
Breast cancer
title Accurate HER2 determination in breast cancer: a prominent COF-immobilized enzyme-enhanced electrochemical aptasensor employing 4-acetamidophenol as an efficient mediator
title_full Accurate HER2 determination in breast cancer: a prominent COF-immobilized enzyme-enhanced electrochemical aptasensor employing 4-acetamidophenol as an efficient mediator
title_fullStr Accurate HER2 determination in breast cancer: a prominent COF-immobilized enzyme-enhanced electrochemical aptasensor employing 4-acetamidophenol as an efficient mediator
title_full_unstemmed Accurate HER2 determination in breast cancer: a prominent COF-immobilized enzyme-enhanced electrochemical aptasensor employing 4-acetamidophenol as an efficient mediator
title_short Accurate HER2 determination in breast cancer: a prominent COF-immobilized enzyme-enhanced electrochemical aptasensor employing 4-acetamidophenol as an efficient mediator
title_sort accurate her2 determination in breast cancer a prominent cof immobilized enzyme enhanced electrochemical aptasensor employing 4 acetamidophenol as an efficient mediator
topic Covalent organic framework
Immobilized enzyme
Electrochemical aptasensing
4-acetamidophenol
Breast cancer
url https://doi.org/10.1186/s12951-024-03035-w
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