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Colorimetric detection of normetanephrine, a pheochromocytoma biomarker, using bifunctionalised gold nanoparticles

DOI:10.1016/j.aca.2019.01.003 期刊:Analytica Chimica Acta 出版年份:2019 更新时间:2025-09-23 15:23:52
摘要: A simple and effective colorimetric method for the detection of normetanephrine (NMN), an O-methylated metabolite of norepinephrine, using functionalised gold nanoparticles is described. This metabolite is an important biomarker in the diagnosis of adrenal tumours such as pheocromocytoma or paraganglioma. The colorimetric probe consists of spherical gold nanoparticles (AuNPs) functionalised with two different ligands, which specifically recognize different functional groups in normetanephrine. Thus, a benzaldehyde-terminated ligand was used for the recognition of the amino alcohol moiety in NMN, by forming the corresponding oxazolidine. On the other hand, N-acetyl-cysteine was chosen for the recognition of the phenolic hydroxyl group through the formation of hydrogen bonds. The selective double molecular recognition between the probe and the hydroxyl and the amino-alcohol moieties of normetanephrine led to interparticle-crosslinking aggregation resulting in a change in the color of the solution, from red to blue, which could be observed by naked eye. The probe was highly selective towards normetanephrine and no color changes were observed in the presence of other neurotransmitter metabolites such as homovanillic acid (HVA) (dopamine metabolite), 5-hydroxyindoleacetic acid (5-HIAA) (serotonin metabolite), or other biomolecules present in urine such as glucose (Glc), uric acid (U.A), and urea. Finally, the probe was evaluated in synthetic urine with constituents that mimic human urine, where a limit of detection of 0.5 mM was achieved.
作者: Tania M. Godoy-Reyes,Ana M. Costero,Pablo Gavi?a,Ramón Martínez-Má?ez,Félix Sancenón
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To develop a simple and effective colorimetric method for the detection of normetanephrine, a biomarker for pheochromocytoma, using bifunctionalised gold nanoparticles.

The developed colorimetric probe GNP1 enables simple, fast, selective, and sensitive detection of normetanephrine with a low limit of detection (0.2 mM in water, 0.52 mM in urine), making it a promising tool for early diagnosis of pheochromocytoma and paraganglioma tumors. Future work should focus on validation in clinical samples and potential integration into point-of-care devices.

The method was tested only in aqueous media and synthetic urine; real human urine samples were not evaluated. The stability and performance in complex biological matrices may require further optimization. The probe's sensitivity might be affected by pH and other environmental factors not fully explored.

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