State Key Laboratory of Food Science and Technology , Nanchang University , Nanchang 330047 , China.
The Second Affiliated Hospital of Nanchang University , Nanchang 330006 , China.
ACS Appl Mater Interfaces. 2018 Apr 25;10(16):14055-14062. doi: 10.1021/acsami.8b02583. Epub 2018 Apr 12.
Studies regarding circulating tumor cells (CTCs) have great significance for cancer prognosis, treatment monitoring, and metastasis diagnosis. However, due to their extremely low concentration in peripheral blood, isolation and enrichment of CTCs are the key steps for early detection. To this end, targeting the folic acid receptors (FRs) on the CTC surface for capture with folic acid (FA) using bovine serum albumin (BSA)-tether for multibiotin enhancement in combination with streptavidin-coated magnetic nanoparticles (MNPs-SA) was developed for ovarian cancer CTC isolation. The streptavidin-biotin-system-mediated two-step binding strategy was shown to capture CTCs from whole blood efficiently without the need for a pretreatment process. The optimized parameters for this system exhibited an average capture efficiency of 80%, which was 25% higher than that of FA-decorated magnetic nanoparticles based on the one-step CTC separation method. Moreover, the isolated cells remained highly viable and were cultured directly without detachment from the MNPs-SA-biotin-CTC complex. Furthermore, when the system was applied for the isolation and detection of CTCs in ovarian cancer patients' peripheral blood samples, it exhibited an 80% correlation with clinical diagnostic criteria. The results indicated that FA targeting, in combination with BSA-based multibiotin enhancement magnetic nanoparticle separation, is a promising tool for CTC enrichment and detection of early-stage ovarian cancer.
循环肿瘤细胞（CTCs）的研究对癌症预后、治疗监测和转移诊断具有重要意义。然而，由于其在外周血中的浓度极低，因此，CTCs 的分离和富集是早期检测的关键步骤。为此，我们开发了一种方法，该方法利用叶酸（FA）靶向 CTC 表面上的叶酸受体（FR），并用牛血清白蛋白（BSA）连接物进行捕获，并用多生物素增强，结合链霉亲和素包被的磁性纳米颗粒（MNPs-SA）用于卵巢癌 CTC 的分离。研究表明，基于两步结合策略的链霉亲和素-生物素系统能够有效捕获全血中的 CTC，而无需预处理过程。该系统的优化参数显示平均捕获效率为 80%，比基于一步 CTC 分离方法的 FA 修饰的磁性纳米颗粒高 25%。此外，分离出的细胞仍然具有高度活力，可以直接在不脱离 MNPs-SA-生物素-CTC 复合物的情况下进行培养。此外，当该系统应用于卵巢癌患者外周血样本中 CTC 的分离和检测时，与临床诊断标准的相关性达到 80%。结果表明，FA 靶向与基于 BSA 的多生物素增强磁性纳米颗粒分离相结合，是一种富集和检测早期卵巢癌 CTC 的有前途的工具。
