Key Laboratory of Magnetic Materials and Devices & Key Laboratory of Additive Manufacturing Materials of Zhejiang Province & Division of Functional Materials and Nanodevices, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences , Ningbo 315201, People's Republic of China.
College of Sciences, Shanghai University , 99 Shangda Road, Shanghai 200444, People's Republic of China.
ACS Appl Mater Interfaces. 2016 Aug 10;8(31):19928-38. doi: 10.1021/acsami.6b07205. Epub 2016 Aug 1.
Circulating tumor cells (CTCs) have received more and more attention in medical biology and clinical practice, especially diagnosis, prognosis, and cancer treatment monitoring. The detection of CTCs within the large number of healthy blood cells is a big challenge due to their rarity, which requires a detection method with supersensitivity and high specificity. In this study, we developed three kinds of new nanoparticles with the function of surface-enhanced Raman scattering (SERS) based on spherical gold nanoparticles (AuNPs), gold nanorods (AuNRs), and gold nanostars (AuNSs) with similar particle size, similar modifications, and different shapes for CTC detection without an enrichment process from the blood. The nanoparticles possess strong SERS signal due to modification of 4-mercaptobenzoic acid (4-MBA) (i.e., Raman reporter molecule), possess excellent specificity due to stabilization of reductive bovine serum albumin (rBSA) to reduce the nonspecific catching or uptake by healthy cells in blood, and possess high sensitivity due to conjugation of folic acid (FA) (i.e., a targeted ligand) to identify CTCs. Under the optimized experimental conditions, the results of detection demonstrate that these nanoparticles could all be utilized for CTC detection without enrichment process from the blood with high specificity, and the AuNS-MBA-rBSA-FA is the best one due to its supersensitivity, whose limit of detection (i.e., 1 cell/mL) is much lower than the currently reported lowest value (5 cells/mL).
循环肿瘤细胞 (CTCs) 在医学生物学和临床实践中受到越来越多的关注，特别是在诊断、预后和癌症治疗监测方面。由于其稀有性，在大量健康血细胞中检测 CTCs 是一个巨大的挑战，这需要一种具有超灵敏度和高特异性的检测方法。在本研究中，我们开发了三种新型纳米粒子，具有表面增强拉曼散射 (SERS) 的功能，基于具有相似粒径、相似修饰但形状不同的球形金纳米粒子 (AuNPs)、金纳米棒 (AuNRs) 和金纳米星 (AuNSs)，用于在没有富集过程的情况下从血液中检测 CTC。纳米粒子由于修饰了 4-巯基苯甲酸 (4-MBA)（即拉曼报告分子）而具有强 SERS 信号，由于还原牛血清白蛋白 (rBSA) 的稳定作用而具有优异的特异性，可以减少血液中健康细胞的非特异性捕获或摄取，并且由于叶酸 (FA) 的共轭（即靶向配体）而具有高灵敏度，用于识别 CTCs。在优化的实验条件下，检测结果表明，这些纳米粒子都可以在没有从血液中富集过程的情况下用于 CTC 检测，具有高特异性，而 AuNS-MBA-rBSA-FA 是最好的一种，因为它具有超灵敏度，其检测限（即 1 个细胞/mL）远低于目前报道的最低值（5 个细胞/mL）。
