基于硼酸盐亲和辅助电化学调控ATRP的癌胚抗原超灵敏电化学适体传感研究

doi:10.13208/j.electrochem.2218001

摘要/Abstract

摘要：

癌胚抗原（CEA）是一种酸性糖蛋白，其作为一种广谱肿瘤标志物在恶性肿瘤的鉴别诊断与监测等方面具有重要价值。在此，借助于硼酸盐亲和辅助电化学调控原子转移自由基聚合（BA-eATRP）的双重信号放大作用，我们报道了一种电化学适体传感器，用于CEA的超灵敏、高选择性检测。基于BA-eATRP的电化学CEA适体传感的基本原理为：待核酸适体捕获CEA抗原后，借助于苯硼酸（PBA）基团与单糖残基上的顺式二醇基团间的选择性亲和相互作用将ATRP引发剂位点靶向性地共价偶联到CEA抗原上；随后，以二茂铁甲基丙烯酸甲酯（FcMMA）作为单体，借助于eATRP将二茂铁（Fc）探针引入电极表面。由于CEA上含有数百个顺式二醇基团，基于硼酸盐亲和的交联反应可使得在每个CEA抗原上标记数百个ATRP引发剂分子。此外，通过eATRP反应，可以在电极表面接枝长的二茂铁基聚合物链，使得每个标记有ATRP引发剂的位点均能连接上成百上千个Fc探针。因此，BA-eATRP可使得每个CEA抗原上标记上大量的Fc探针。在最佳条件下，基于BA-eATRP的电化学适体传感器能够实现浓度低为0.34 pg·mL^-1的CEA的高选择性检测，其线性范围为1.0-1000 pg·mL^-1。而且，该适体传感器可用于人血清中CEA的定量分析。基于BA-eATRP的电化学适体传感器具有成本低廉、操作简便等优良特性，在CEA的超灵敏、高选择性检测方面具有广阔的应用前景。

关键词: 硼酸盐亲和, 原子转移自由基聚合, 电化学适体传感器, 癌胚抗原, 肿瘤标志物, 信号放大

Abstract:

As an acidic glycoprotein, carcinoembryonic antigen (CEA) is of great value as a broad-spectrum tumor marker in the differential diagnosis and surveillance of malignant tumors. In this work, we report an electrochemical aptasensor for the ultrasensitive and highly selective detection of CEA, taking advantage of the dual amplification by the boronate affinity-assisted electrochemically controlled atom transfer radical polymerization (BA-eATRP). Specifically, the BA-eATRP-based electrochemical aptasensing of CEA involves the capture of target antigens by nucleic acid aptamers, the covalent crosslinking of ATRP initiators to CEA antigens via the selective interactions between the phenylboronic acid (PBA) group and the cis-diol group of the monosaccharide residues, and the collection of the ferrocene (Fc) reporters via the eATRP of ferrocenylmethyl methacrylate (FcMMA). As CEA is decorated with hundreds of cis-diol groups, the BA-based crosslinking can result in the labeling of each CEA with hundreds of ATRP initiators; furthermore, the eATRP of FcMMA results in the surface-initiated growth of long-chain ferrocenyl polymers, leading to the tethering of each ATRP initiator-conjugated site with hundreds to thousands of Fc reporters. Such that, the BA-eATRP can result in the efficient labeling of each CEA with a plenty of Fc reporters. Under the optimized conditions, the BA-eATRP-based strategy enables the highly selective aptasensing of CEA at a concentration as low as 0.34 pg·mL^-1, with a linear range of 1.0-1,000 pg·mL^-1. Besides, this aptasensor has been successfully applied to the quantitative analysis of CEA in human serum. The BA-eATRP-based electrochemical aptasensor is cost-effective and simple in operation, holding broad application prospect in the ultrasensitive and highly selective detection of CEA.

Key words: boronate affinity, atom transfer radical polymerization, electrochemical aptasensor, carcinoembryonic antigen, tumor marker, signal amplification

胡琼, 李诗琪, 梁伊依, 冯文星, 骆怡琳, 曹晓静, 牛利. 基于硼酸盐亲和辅助电化学调控ATRP的癌胚抗原超灵敏电化学适体传感研究[J]. 电化学（中英文）, 2023, 29(6): 2218001.

Qiong Hu, Shi-Qi Li, Yi-Yi Liang, Wen-Xing Feng, Yi-Lin Luo, Xiao-Jing Cao, Li Niu. Boronate Affinity-Assisted Electrochemically Controlled ATRP for Ultrasensitive Electrochemical Aptasensing of Carcinoembryonic Antigen[J]. Journal of Electrochemistry, 2023, 29(6): 2218001.

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链接本文: https://electrochem.xmu.edu.cn/CN/10.13208/j.electrochem.2218001

https://electrochem.xmu.edu.cn/CN/Y2023/V29/I6/2218001

图/表 9

参考文献 57

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Sample	Added (pg·mL⁻¹)	Found (pg·mL⁻¹)	Recovery	RSD (n = 5)
1	1,000	943.0	94.3%	5.2%
2	100	103.5	103.5%	5.4%
3	10	10.55	105.5%	5.8%