Miao Chenfang, Zhang Menghan, Zheng Ying, Lin Xiaoyan, Yang Shuangying, Xu Linlin, Lu Sitong, Huang Zhengjun, Huang Jianyong, Zheng Yanjie, Weng Shaohuang
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, China.
Mater Today Bio. 2025 Jun 23;33:102019. doi: 10.1016/j.mtbio.2025.102019. eCollection 2025 Aug.
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 (HO), which subsequently reacted with Fe 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.
氨茶碱（AMP）是一种黄嘌呤衍生的支气管扩张剂，治疗窗较窄，为安全用药需要及时进行血药浓度监测和药代动力学（PK）研究。然而，高效且灵敏的检测方法仍然有限。在本研究中，以核黄素为碳源、柠檬酸和乙二胺为功能化剂及掺杂剂，通过水热法合成了高量子产率的碳点（CA/EDA-CDs）。CA/EDA-CDs的发光结构具有π共轭体系（芳香族C=C和石墨N）以及通过C-N、C-O和氢键连接的表面发色团（C=N/C=O），可通过羟基自由基（·OH）进行可控调制。在暴露于·OH时，CA/EDA-CDs在3.52 eV和5.21 eV处的发射带隙消失，同时出现了一个2.63 eV的新能级，导致CA/EDA-CDs对·OH产生定量且选择性的荧光猝灭。利用黄嘌呤氧化酶（XOD）介导的AMP氧化为过氧化氢（HO），后者随后与Fe反应生成·OH，构建了一种以CA/EDA-CDs为探针的灵敏且准确的荧光方法用于监测AMP，性能优异。此外，所开发的荧光策略被可控地应用于静脉注射AMP（11.25 mg/kg和22.50 mg/kg）的大鼠的PK研究，得到的参数与临床数据一致。这些发现凸显了CA/EDA-CDs在快速准确检测AMP方面的潜力，满足了临床对简单快速监测方法的需求。
