Li Na, Li Xian, Ming Xiaoe, Chen Jingyuan, Chen Yeyi, Zhou Lifen, Yao Ruirui, Yao Yuqi
Pharmaceutical College, Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, Key Laboratory of Micro-Nanoscale Bioanalysis and Drug Screening of Guangxi Higher Education, Guangxi Medical University, Nanning, 530021, China.
Pharmaceutical College, Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, Key Laboratory of Micro-Nanoscale Bioanalysis and Drug Screening of Guangxi Higher Education, Guangxi Medical University, Nanning, 530021, China.
Talanta. 2025 Feb 1;283:127116. doi: 10.1016/j.talanta.2024.127116. Epub 2024 Oct 30.
Deferasirox (DEF) is an important iron chelator for treatment of iron overload-related diseases. Monitoring DEF concentration in human serum will provide some valuable information for clinical diagnosis and therapy of such diseases. In this study, we developed a peroxidase-mimicking colorimetric sensor for the detection of DEF by simple assembly of a telomeric dimeric G-quadruplex DNAzyme with Cu. The DNAzyme-catalyzed oxidation of 3,3',5,5'-tetramethylbenzidine in the presence of HO can generate a quantitative colorimetric signal, and the color change can be discerned by the naked eye. Compared with the reaction rate of the monomeric G-quadruplex-Cu DNAzyme, the reaction rate of the dimeric G-quadruplex-Cu (G2-Cu) DNAzyme is significantly accelerated, and the reaction rate gradually increases and then reaches a plateau with increasing number of TTA spacers. Herein, the G2-Cu DNAzyme is chosen for the highly sensitive detection of DEF based on the DEF-Cu complex-induced inhibition of its peroxidase-mimicking activities. The limit of detection (LOD) of DEF is achieved as low as 0.03 μM, and the linear range is from 0.05 to 1.2 μM. The proposed strategy exhibits excellent selectivity in the presence of potential interferents, such as metal ions and small molecules. Importantly, the G2-Cu DNAzyme is further expanded to detect DEF in dispersible tablets and human serum samples. Overall, this G2-Cu DNAzyme provides a simple, low-cost, and rapid platform for DEF detection. This novel strategy is the first example of DEF analysis by utilizing signal amplification technology based on the G-quadruplex DNAzyme and holds great potential for DEF quality control and therapeutic drug monitoring.
地拉罗司（DEF）是治疗铁过载相关疾病的重要铁螯合剂。监测人体血清中的DEF浓度将为这类疾病的临床诊断和治疗提供一些有价值的信息。在本研究中，我们通过将端粒二聚体G-四链体DNAzyme与铜简单组装，开发了一种用于检测DEF的过氧化物酶模拟比色传感器。在过氧化氢存在下，DNAzyme催化3,3',5,5'-四甲基联苯胺氧化可产生定量的比色信号，且颜色变化可用肉眼辨别。与单体G-四链体-铜DNAzyme的反应速率相比，二聚体G-四链体-铜（G2-Cu）DNAzyme的反应速率显著加快，且随着TTA间隔序列数量增加，反应速率逐渐上升然后达到平稳状态。在此，基于DEF-铜复合物对其过氧化物酶模拟活性的抑制作用，选择G2-Cu DNAzyme用于DEF的高灵敏度检测。DEF的检测限低至0.03 μM，线性范围为0.05至1.2 μM。所提出的策略在存在潜在干扰物（如金属离子和小分子）的情况下表现出优异的选择性。重要的是，G2-Cu DNAzyme进一步扩展用于检测分散片和人体血清样品中的DEF。总体而言，这种G2-Cu DNAzyme为DEF检测提供了一个简单、低成本且快速的平台。这种新颖的策略是利用基于G-四链体DNAzyme的信号放大技术进行DEF分析的首个实例，在DEF质量控制和治疗药物监测方面具有巨大潜力。
