CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, No. 457 Zhongshan Road, Dalian 116023, China.
College of Information Science and Engineering, Northeastern University, Shenyang 110819, China.
Biosensors (Basel). 2024 Sep 9;14(9):436. doi: 10.3390/bios14090436.
Estrogenic chemicals are widely distributed and structurally diverse. They primarily disrupt estrogen-related metabolism in animals or humans by mimicking the agonistic receptor effects of natural estrogens, thereby influencing the transcription of estrogen receptors to regulate their quantity and sensitivity. This disruption of estrogen-related metabolism can lead to estrogen-related effects, posing risks to biological health, emphasizing the urgent need for simple and effective methods to screen compounds with estrogenic effects. Herein, a new electrochemical biological effect biosensor based on human estrogen receptor α (hERα) is developed, which uses hERα as the biorecognition element and employs the electroactive horseradish peroxidase (HRP) labeled 17β-estradiol (E2) multifunctional conjugate HRP-E2 as the signal-boosting element and ligand competition agent. Based on the specific ligand-receptor interaction principle between the target and nuclear receptor, by allowing the test compound to compete with HRP-E2 conjugate for binding to hERα and testing the electrocatalytic signal of the conjugate that fails to bind to the hERα estrogen receptor, rapid screening and quantitative detection of chemical substances with estrogenic effect have been achieved. The biosensor shows a wide linear range of 40 pM to 40 nM with a detection limit of 17 pM (S/N = 3) for E2, and the detection limit is 2 orders of magnitude better than that of the previously reported sensors. The biosensor based on ligand-receptor binding can not only quantitatively analyze the typical estrogen E2, but also evaluate the relative estrogen effect strength of other estrogen compounds, which has good stability and selectivity. This electrochemical sensing platform displays its promising potential for rapid screening and quantitative detection of chemicals with estrogenic effects.
雌激素类化学物质分布广泛,结构多样。它们主要通过模拟天然雌激素的激动受体作用来干扰动物或人类的雌激素相关代谢,从而影响雌激素受体的转录,调节其数量和敏感性。这种雌激素相关代谢的干扰会导致雌激素相关效应,对生物健康构成威胁,强调了迫切需要简单有效的方法来筛选具有雌激素效应的化合物。在此,开发了一种基于人雌激素受体α(hERα)的新型电化学生物效应生物传感器,该传感器将 hERα 用作生物识别元件,并采用辣根过氧化物酶(HRP)标记的 17β-雌二醇(E2)多功能缀合物 HRP-E2 作为信号增强元件和配体竞争剂。基于目标和核受体之间特定的配体-受体相互作用原理,允许测试化合物与 HRP-E2 缀合物竞争与 hERα 结合,并测试未能与 hERα 雌激素受体结合的缀合物的电化学催化信号,从而实现了对具有雌激素效应的化学物质的快速筛选和定量检测。该生物传感器对 E2 的线性范围为 40 pM 至 40 nM,检测限为 17 pM(S/N = 3),检测限比以前报道的传感器好 2 个数量级。基于配体-受体结合的生物传感器不仅可以定量分析典型的雌激素 E2,还可以评估其他雌激素化合物的相对雌激素效应强度,具有良好的稳定性和选择性。这种电化学传感平台显示出其在快速筛选和定量检测具有雌激素效应的化学物质方面的广阔应用前景。