National and Local United Engineering Lab of Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006, China.
ACS Sens. 2024 Oct 25;9(10):5354-5362. doi: 10.1021/acssensors.4c01594. Epub 2024 Oct 17.
Monitoring biomarkers secreted by cardiomyocytes is critical to evaluate anticancer drug-induced myocardial injury (MI). Cardiac troponin I (cTnI) is considered the gold standard biomarker for MI. Herein, an electrochemical aptasensor is engineered for cTnI detection based on lanthanide europium metal-organic frameworks (Eu-MOFs) and a hybridization chain reaction-directed DNAzyme strategy. Three types of Eu-MOF morphologies were easily synthesized by changing the solvent, and the Eu-MOF modulated by mixing the solvent of dimethylformamide and HO (D-Eu-MOF) exhibited the best performance compared to other morphologies of the Eu-MOFs. Multifunctional nanoprobes were constructed from D-Eu-MOF@Pt loaded with natural horseradish peroxidase and combined with an aptamer-initiated nuclear acid hybridization chain reaction to form G-quadruplex/hemin DNAzymes for signal amplification. A novel capture probe is constructed on the basis of DNA nanotetrahedrons modified on screen-printed gold electrodes to enhance the capture of the target and multifunctional nanoprobes for signal amplification. It exhibits a detection limit of 0.17 pg mL and a linear range from 0.5 pg mL to 15 ng mL. The practicality of the platform is evaluated by measuring cTnI in real samples and secreted by cardiomyocytes after drug treatment, which provides great potential in drug-induced MI evaluation for clinical application.
监测心肌细胞分泌的生物标志物对于评估抗癌药物诱导的心肌损伤（MI）至关重要。心肌肌钙蛋白 I（cTnI）被认为是 MI 的金标准生物标志物。本文基于镧系金属有机框架（Eu-MOFs）和杂交链式反应导向的 DNA 酶策略，设计了一种用于 cTnI 检测的电化学适体传感器。通过改变溶剂，很容易合成三种类型的 Eu-MOF 形态，与其他 Eu-MOF 形态相比，Eu-MOF 混合溶剂的调制（D-Eu-MOF）表现出最佳性能。从装载天然辣根过氧化物酶的 D-Eu-MOF@Pt 构建多功能纳米探针，并与适体引发的核酸杂交链式反应结合，形成 G-四链体/血红素 DNA 酶进行信号放大。基于修饰在丝网印刷金电极上的 DNA 四面体构建了一种新型捕获探针，以增强对目标和多功能纳米探针的捕获，用于信号放大。它的检测限为 0.17 pg mL，线性范围为 0.5 pg mL 至 15 ng mL。该平台通过测量药物处理后心肌细胞分泌的实际样品中的 cTnI 进行了实用性评估，为临床应用中药物诱导的 MI 评估提供了巨大潜力。
