Wang Zixia, Chen Mian, Li Diaoguo, Sun Bolu, Kang Jiali, He Haiying, Lv Ying, Da Xuanxiu, Zhou Miao, Wu Yong
Department of Pharmacy, The Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, 225001, People's Republic of China.
College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, Gansu, 730000, People's Republic of China.
Mikrochim Acta. 2025 Sep 17;192(10):674. doi: 10.1007/s00604-025-07482-6.
Drug-induced cardiotoxicity (DIC) poses a significant challenge in both drug development and clinical practice, Making early and accurate assessment crucial. Existing studies have shown that mitochondrial fusion mediated by mitochondrial fusion protein 2 (Mfn2) is closely associated with DIC, and that upregulation of Mfn2 reduces drug-induced cardiomyocyte damage and apoptosis, suggesting that Mfn2 could be a potential biomarker for early warning assessment of DIC. Due to the defects of cumbersome operation, limited sensitivity, high cost, and difficulty in popularization of existing detection technologies, this study pioneers a novel electrochemical immunosensor for highly sensitive Mfn2 detection using a composite sensing substrate of MXene-derived sodium titanate nanorods and multi-walled carbon nanotubes (M-NTO-MWCNT). This technology enables early warning and assessment of drug-induced cardiotoxicity. The M-NTO component, with its unique nanorod structure, abundant active sites, and high surface area, significantly enhances sensitivity and provides abundant antibody immobilization sites. Meanwhile, MWCNTs improve electron transfer efficiency and selectivity due to their superior conductivity and interconnected network. Under optimized conditions, the sensor achieves a detection Limit as low as 1.85 ng mL and a Linear range of 9.38 × 10-2.40 × 10 ng mL. Serum sample testing demonstrated excellent reproducibility (RSD < 5%), outperforming conventional ELISA methods. This study provides a new rapid and highly sensitive test solution for the early warning of drug-derived cardiotoxicity, offering technical support and scientific basis for safety assessment in new drug development.
药物性心脏毒性（DIC）在药物研发和临床实践中都构成了重大挑战，因此早期准确评估至关重要。现有研究表明，由线粒体融合蛋白2（Mfn2）介导的线粒体融合与DIC密切相关，且Mfn2的上调可减少药物诱导的心肌细胞损伤和凋亡，这表明Mfn2可能是DIC早期预警评估的潜在生物标志物。由于现有检测技术操作繁琐、灵敏度有限、成本高且难以推广等缺陷，本研究开创性地使用由MXene衍生的钛酸钠纳米棒和多壁碳纳米管（M-NTO-MWCNT）组成的复合传感基底，开发了一种用于高灵敏度检测Mfn2的新型电化学免疫传感器。该技术能够对药物性心脏毒性进行早期预警和评估。M-NTO组分具有独特的纳米棒结构、丰富的活性位点和高比表面积，显著提高了灵敏度并提供了丰富的抗体固定位点。同时，多壁碳纳米管因其优异的导电性和互连网络提高了电子转移效率和选择性。在优化条件下，该传感器的检测限低至1.85 ng/mL，线性范围为9.38×10⁻² - 4.0×10² ng/mL。血清样本检测显示出优异的重现性（RSD＜5%），优于传统酶联免疫吸附测定（ELISA）方法。本研究为药物源性心脏毒性的早期预警提供了一种新的快速且高灵敏度的检测解决方案，为新药研发中的安全性评估提供了技术支持和科学依据。
