An effective fluorescence strategy based on xanthine oxidase catalysis and the carbon dots’ specific response to ·OH for aminophylline pharmacokinetic studies

Aminophylline (AMP), a xanthine-derived bronchodilator with a narrow therapeutic window, requires timely plasma concentration monitoring and pharmacokinetic (PK) studies for safe medication. However, efficient and sensitive detection methods remain limited. In this study, high quantum yield carbon d...

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Main Authors: Chenfang Miao, Menghan Zhang, Ying Zheng, Xiaoyan Lin, Shuangying Yang, Linlin Xu, Sitong Lu, Zhengjun Huang, Jianyong Huang, Yanjie Zheng, Shaohuang Weng
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425005897
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author Chenfang Miao
Menghan Zhang
Ying Zheng
Xiaoyan Lin
Shuangying Yang
Linlin Xu
Sitong Lu
Zhengjun Huang
Jianyong Huang
Yanjie Zheng
Shaohuang Weng
author_facet Chenfang Miao
Menghan Zhang
Ying Zheng
Xiaoyan Lin
Shuangying Yang
Linlin Xu
Sitong Lu
Zhengjun Huang
Jianyong Huang
Yanjie Zheng
Shaohuang Weng
author_sort Chenfang Miao
collection DOAJ
description Aminophylline (AMP), a xanthine-derived bronchodilator with a narrow therapeutic window, requires timely plasma concentration monitoring and pharmacokinetic (PK) studies for safe medication. However, efficient and sensitive detection methods remain limited. In this study, high quantum yield carbon dots (CA/EDA-CDs) were synthesized via a hydrothermal method using riboflavin as the carbon source, citric acid and ethylenediamine as functionalizing agents and dopants. The luminescent structure of CA/EDA-CDs, featuring a π-conjugated system (aromatic C=C and graphite N) and surface chromophores (C=N/C=O) connected via C-N, C-O, and hydrogen bonds, was controllably modulated by hydroxyl radical (·OH). Upon ·OH exposure, the emission band gaps of CA/EDA-CDs at 3.52 eV and 5.21 eV disappeared, while a new level at 2.63 eV emerged, leading to a quantitative and selective fluorescence quenching of CA/EDA-CDs to ·OH. Leveraging xanthine oxidase (XOD)-mediated AMP oxidation to hydrogen peroxide (H2O2), which subsequently reacted with Fe2+ to generate ·OH, a sensitive and accurate fluorescence method using CA/EDA-CDs as probe was fabricated for monitoring AMP with excellent performance. Furthermore, the developed fluorescence strategy was controllably applied to PK studies in rats administered intravenous AMP (11.25 mg/kg and 22.50 mg/kg), yielding parameters consistent with clinical data. These findings underscore the potential of CA/EDA-CDs for rapid and accurate AMP detection, addressing the clinical need for a simple and rapid monitoring method.
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spelling doaj-art-c4e0aad23d684f33b5eecec7e4d478762025-08-20T03:26:56ZengElsevierMaterials Today Bio2590-00642025-08-013310201910.1016/j.mtbio.2025.102019An effective fluorescence strategy based on xanthine oxidase catalysis and the carbon dots’ specific response to ·OH for aminophylline pharmacokinetic studiesChenfang Miao0Menghan Zhang1Ying Zheng2Xiaoyan Lin3Shuangying Yang4Linlin Xu5Sitong Lu6Zhengjun Huang7Jianyong Huang8Yanjie Zheng9Shaohuang Weng10Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, ChinaDepartment of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, ChinaDepartment of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, ChinaDepartment of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, ChinaDepartment of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, ChinaDepartment of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, ChinaDepartment of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, ChinaDepartment of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, China; The Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, Fujian Medical University, Fuzhou, 350122, ChinaDepartment of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, 350001, China; Corresponding author.Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, China; The Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, Fujian Medical University, Fuzhou, 350122, ChinaDepartment of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, China; The Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, Fujian Medical University, Fuzhou, 350122, China; Corresponding author. Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, China.Aminophylline (AMP), a xanthine-derived bronchodilator with a narrow therapeutic window, requires timely plasma concentration monitoring and pharmacokinetic (PK) studies for safe medication. However, efficient and sensitive detection methods remain limited. In this study, high quantum yield carbon dots (CA/EDA-CDs) were synthesized via a hydrothermal method using riboflavin as the carbon source, citric acid and ethylenediamine as functionalizing agents and dopants. The luminescent structure of CA/EDA-CDs, featuring a π-conjugated system (aromatic C=C and graphite N) and surface chromophores (C=N/C=O) connected via C-N, C-O, and hydrogen bonds, was controllably modulated by hydroxyl radical (·OH). Upon ·OH exposure, the emission band gaps of CA/EDA-CDs at 3.52 eV and 5.21 eV disappeared, while a new level at 2.63 eV emerged, leading to a quantitative and selective fluorescence quenching of CA/EDA-CDs to ·OH. Leveraging xanthine oxidase (XOD)-mediated AMP oxidation to hydrogen peroxide (H2O2), which subsequently reacted with Fe2+ to generate ·OH, a sensitive and accurate fluorescence method using CA/EDA-CDs as probe was fabricated for monitoring AMP with excellent performance. Furthermore, the developed fluorescence strategy was controllably applied to PK studies in rats administered intravenous AMP (11.25 mg/kg and 22.50 mg/kg), yielding parameters consistent with clinical data. These findings underscore the potential of CA/EDA-CDs for rapid and accurate AMP detection, addressing the clinical need for a simple and rapid monitoring method.http://www.sciencedirect.com/science/article/pii/S2590006425005897Carbon dotsHydroxyl radicalSpecific responseFluorescence strategyPharmacokinetic studyAminophylline
spellingShingle Chenfang Miao
Menghan Zhang
Ying Zheng
Xiaoyan Lin
Shuangying Yang
Linlin Xu
Sitong Lu
Zhengjun Huang
Jianyong Huang
Yanjie Zheng
Shaohuang Weng
An effective fluorescence strategy based on xanthine oxidase catalysis and the carbon dots’ specific response to ·OH for aminophylline pharmacokinetic studies
Materials Today Bio
Carbon dots
Hydroxyl radical
Specific response
Fluorescence strategy
Pharmacokinetic study
Aminophylline
title An effective fluorescence strategy based on xanthine oxidase catalysis and the carbon dots’ specific response to ·OH for aminophylline pharmacokinetic studies
title_full An effective fluorescence strategy based on xanthine oxidase catalysis and the carbon dots’ specific response to ·OH for aminophylline pharmacokinetic studies
title_fullStr An effective fluorescence strategy based on xanthine oxidase catalysis and the carbon dots’ specific response to ·OH for aminophylline pharmacokinetic studies
title_full_unstemmed An effective fluorescence strategy based on xanthine oxidase catalysis and the carbon dots’ specific response to ·OH for aminophylline pharmacokinetic studies
title_short An effective fluorescence strategy based on xanthine oxidase catalysis and the carbon dots’ specific response to ·OH for aminophylline pharmacokinetic studies
title_sort effective fluorescence strategy based on xanthine oxidase catalysis and the carbon dots specific response to ·oh for aminophylline pharmacokinetic studies
topic Carbon dots
Hydroxyl radical
Specific response
Fluorescence strategy
Pharmacokinetic study
Aminophylline
url http://www.sciencedirect.com/science/article/pii/S2590006425005897
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