Zhanjiang Institute of Clinical Medicine, Central People's Hospital of Zhanjiang, Guangdong Medical University Zhanjiang Central Hospital, Zhanjiang, 524045, China; College of Pharmacy, China Pharmaceutical University, Nanjing, 211198, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, Key Laboratory of Animal Bacteriology, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
College of Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
Talanta. 2023 Dec 1;265:124927. doi: 10.1016/j.talanta.2023.124927. Epub 2023 Jul 7.
Protein glycosylation and other post-translational modifications are involved in many biological processes including growth, development and immune responses, and glycoproteins are also known as biomarkers for cancer, diabetes and cardiovascular diseases. In traditional lateral flow immunoassay (LFIA) for glycoprotein detection, capture antibody (CA) is often required to label targets. However, the production of CA is complicated and expensive, restricting the wide application of LFIA. In this study, we developed a universal boronate affinity CA-independent LFIA method for glycoprotein detection. 4-Mercaptophenylboronic acid (4-MPBA)-modified Au nanoparticles (namely 4-MPBA-AuNPs) were used as LFIA labels, which could generate colorimetric signal and showed outstanding capability to bind glycoprotein. Compared with CA, 4-MPBA molecular as a glycoprotein recognition element had more prominent advantages, e.g., low cost, easy availability and good quality controllability. Take carcinoembryonic antigen (CEA) as model glycoprotein, the limit of detection of this CA-independent LFIA was 1.25 ng/mL by naked eyes, which was 8-fold lower than conventional CA-dependent sandwich LFIA. Significantly, the developed 4-MPBA-AuNPs-based CA-independent LFIA successfully detected 23 CEA-positive samples from 64 suspected human serum samples within 50 min in a nonlaboratory environment, with a 100% accuracy compared to clinical detection method. Therefore, this diagnostic platform could provide an effective tool for point-of-care glycoprotein detection with excellent reproducibility and high specificity.
蛋白质糖基化和其他翻译后修饰参与许多生物过程,包括生长、发育和免疫反应,糖蛋白也被称为癌症、糖尿病和心血管疾病的生物标志物。在传统的用于糖蛋白检测的侧向流动免疫分析(LFIA)中,通常需要捕获抗体(CA)来标记靶标。然而,CA 的生产既复杂又昂贵,限制了 LFIA 的广泛应用。在这项研究中,我们开发了一种用于糖蛋白检测的通用硼酸亲和 CA 独立 LFIA 方法。4-巯基苯硼酸(4-MPBA)修饰的金纳米粒子(即 4-MPBA-AuNPs)被用作 LFIA 标记物,可产生比色信号,并表现出出色的结合糖蛋白的能力。与 CA 相比,4-MPBA 分子作为糖蛋白识别元件具有更突出的优势,例如成本低、易得和良好的质量可控性。以癌胚抗原(CEA)为模型糖蛋白,该 CA 独立 LFIA 的检测限通过肉眼观察为 1.25ng/mL,比传统的 CA 依赖夹心 LFIA 低 8 倍。值得注意的是,在非实验室环境下,该开发的基于 4-MPBA-AuNPs 的 CA 独立 LFIA 在 50 分钟内成功检测了 64 份疑似人血清样本中的 23 份 CEA 阳性样本,与临床检测方法相比,准确率为 100%。因此,该诊断平台为即时检测糖蛋白提供了一种有效的工具,具有良好的重现性和高特异性。