Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China.
Tianjin International Engineering Institute, Tianjin University, Tianjin 300072, China.
ACS Appl Bio Mater. 2021 Jul 19;4(7):5494-5502. doi: 10.1021/acsabm.1c00324. Epub 2021 Jun 29.
Metal-organic frameworks (MOFs) are composed of metal ions/clusters and organic ligands, showing accessible functional sites, ultra-high porosity, and large specific surface area. Tricopper benzene-1,3,5-tricarboxylate (CuBTC), as a three-dimensional MOF architecture with an open and robust micro-/nanoconfiguration, possesses excellent catalytic performance and superior electric conductivity as compared to bulk MOF. In this study, CuBTC was used as a substrate on which molybdenum disulfide (MoS) was in situ constructed by a hydrothermal reaction to enhance the electron- and ion-transfer capability. Then, gold nanoparticles (AuNPs) were electroreduced on a CuBTC@MoS-modified electrode by linear sweep voltammetry for strengthening the connection between CA125 antibodies (CA125 Ab) and the substrate material. Due to the synergistic effect of CuBTC@MoS and AuNPs, our biosensor showed excellent electrochemical performance. Subsequently, CuBTC@MoS-AuNPs/CA125 Ab-functionalized electrodes were used for the detection of the ovarian cancer biomarker CA125 from 0.5 mU/mL to 500 U/mL by differential pulse voltammetry. The results showed that the peak current decreased with the increase of concentration, and there was a logistic regression relationship between peak current variation and concentration. As interfering substances, carcinoembryonic antigen, human epididymis protein 4, and bovine serum albumin were applied for specific analysis. Our biosensor showed an obviously large response signal for CA125 detection than those observed for other interfering substances. Finally, serum samples collected from five patients were tested on our sensors with good consistency toward clinical standards, showing high practicability. This work demonstrated a tactic for simultaneously integrating the nanostructure, electroconductivity, and biocompatibility to construct advanced biosensors for cancer biomarkers.
金属有机骨架（MOFs）由金属离子/簇和有机配体组成，具有可及的功能位点、超高的孔隙率和大的比表面积。三铜苯-1,3,5-三甲酸（CuBTC）作为一种具有开放和坚固的微/纳米结构的三维 MOF 架构，与体相 MOF 相比，具有优异的催化性能和卓越的导电性。在这项研究中，CuBTC 被用作基底，通过水热反应原位构建二硫化钼（MoS），以增强电子和离子传输能力。然后，通过线性扫描伏安法在 CuBTC@MoS 修饰电极上电还原金纳米颗粒（AuNPs），以加强 CA125 抗体（CA125 Ab）与基底材料之间的连接。由于 CuBTC@MoS 和 AuNPs 的协同作用，我们的生物传感器表现出优异的电化学性能。随后，使用 CuBTC@MoS-AuNPs/CA125 Ab 功能化电极通过差分脉冲伏安法检测卵巢癌标志物 CA125 的浓度范围为 0.5 mU/mL 至 500 U/mL。结果表明，随着浓度的增加，峰电流减小，峰电流变化与浓度之间存在逻辑回归关系。作为干扰物质，癌胚抗原、人附睾蛋白 4 和牛血清白蛋白被用于特异性分析。与观察到的其他干扰物质相比，我们的生物传感器对 CA125 的检测表现出明显更大的响应信号。最后，用我们的传感器测试了来自五名患者的血清样本，与临床标准具有良好的一致性，表现出很高的实用性。这项工作展示了一种同时整合纳米结构、导电性和生物相容性的策略，用于构建用于癌症生物标志物的先进生物传感器。
