Lu Yulin, Liu Qunshan, Fu Bangguo, Li Pan, Xu Weiping
Department of Geriatrics, Institute of Gerontology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230031, China.
Talanta. 2023 Jun 1;258:124461. doi: 10.1016/j.talanta.2023.124461. Epub 2023 Mar 21.
Early diagnosis of colorectal cancer can significantly improve the overall survival rate of patients, thus selective and sensitive detection of biomarkers in serum samples is vital for early detection and dynamic monitoring of cancer. Nucleoside diphosphate kinase NM23-H2 (NDKB) is an important biomarker and therapeutic target for the diagnosis of colorectal cancer (CRC). Here, a label-free and ultrasensitive biosensor for NDKB protein markers is presented for the first time, combining the characteristic capture selectivity of molecularly imprinted polymers (MIPs) and the ultrasensitivity of surface-enhanced Raman Spectroscopy (SERS) technique. The imprinted cavity serves as the only channel for Raman reporter to approach the SERS substrate, providing highly complementary non-covalent binding sites that selectively capture the target protein based on ionic, hydrogen bonding or hydrophobic interactions. Specific recognition of the NDKB protein will perfectly fill the imprinted cavity, which makes it difficult for the Raman reporter to get close to the SERS substrate, and the Raman signal decreases significantly, while the proteins of other structural sizes can not match the imprinted cavity. Through the change of the Raman signal, the proposed biosensor can realize the ultra-sensitive detection of NDKB, and the limit of detection (LOD) is 0.82 pg/mL. Compared with the traditional immunoassay technology, this combined approach with the advantages of low cost, fast response, high sensitivity and selectivity, provides clinical application potential for the early diagnosis of CRC.
结直肠癌的早期诊断可显著提高患者的总体生存率，因此血清样本中生物标志物的选择性和灵敏检测对于癌症的早期检测和动态监测至关重要。核苷二磷酸激酶NM23-H2（NDKB）是结直肠癌（CRC）诊断的重要生物标志物和治疗靶点。在此，首次提出了一种用于NDKB蛋白标志物的无标记超灵敏生物传感器，它结合了分子印迹聚合物（MIPs）的特征捕获选择性和表面增强拉曼光谱（SERS）技术的超灵敏性。印迹腔作为拉曼报告分子接近SERS底物的唯一通道，提供高度互补的非共价结合位点，基于离子、氢键或疏水相互作用选择性捕获目标蛋白。对NDKB蛋白的特异性识别将完美填充印迹腔，这使得拉曼报告分子难以接近SERS底物，拉曼信号显著降低，而其他结构大小的蛋白质无法匹配印迹腔。通过拉曼信号的变化，所提出的生物传感器可实现对NDKB的超灵敏检测，检测限（LOD）为0.82 pg/mL。与传统免疫分析技术相比，这种结合方法具有低成本、响应快、灵敏度高和选择性好等优点，为CRC的早期诊断提供了临床应用潜力。
