Quick-Response Magnetic Nanospheres for Rapid, Efficient Capture and Sensitive Detection of Circulating Tumor Cells

Quick-Response Magnetic Nanospheres for Rapid, Efficient Capture and Sensitive Detection of Circulating Tumor Cells
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快速响应磁性纳米球,用于快速、高效捕获和灵敏检测循环肿瘤细胞

DOI:
10.1021/nn405744f
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发表时间:
2014-01-01
期刊:
影响因子:
17.1
通讯作者:
Pang, Dai-Wen
Pang, Dai-Wen
中科院分区:
材料科学1区
文献类型:
--
作者:
Wen, Cong-Ying;Wu, Ling-Ling;Pang, Dai-Wen

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循环肿瘤细胞(CTC)的研究对于癌症预后、治疗监测和转移诊断具有重要意义,其中由于CTC在外周血中浓度极低,其分离和富集是关键步骤。在此,磁性纳米球(MN)是通过一种方便且高度可控的逐层组装方法制造的。 MNs 是纳米尺寸的,具有快速磁响应,并且几乎所有的 MNs 都可以通过商业磁性支架 1 分钟的吸引来捕获。此外,MNs非常稳定,在全血中不会聚集或沉淀,并且可以以单分散状态几乎100%地重新收集。用抗上皮细胞粘附分子(EpCAM)抗体修饰,获得的免疫磁性纳米球(IMN)仅通过5分钟的孵育就成功捕获了全血中极其罕见的肿瘤细胞,效率超过94%。此外,分离的细胞存活率为90.5 +/- 1.2%,可直接用于培养、逆转录聚合酶链反应(RT-PCR)和免疫细胞化学(ICC)鉴定。 ICC对同一血样中肿瘤细胞的鉴定和计数显示出高灵敏度和良好的重现性。此外,IMNs已成功应用于癌症患者外周血样本中CTC的分离和检测,甚至能够检测到全血样本中的CTC,这表明它们将成为CTC富集和检测的有前途的工具。
The study on circulating tumor cells (CTCs) has great significance for cancer prognosis, treatment monitoring, and metastasis diagnosis, in which isolation and enrichment of CTCs are key steps due to their extremely low concentration in peripheral blood. Herein, magnetic nanospheres (MNs) were fabricated by a convenient and highly controllable layer-by-layer assembly method. The MNs were nanosized with fast magnetic response, and nearly all of the MNs could be captured by 1 min attraction with a commercial magnetic scaffold. In addition, the MNs were very stable without aggregation or precipitation in whole blood and could be re-collected nearly at 100% in a monodisperse state. Modified with anti-epithelial-cell-adhesion-molecule (EpCAM) antibody, the obtained immunomagnetic nanospheres (IMNs) successfully captured extremely rare tumor cells in whole blood with an efficiency of more than 94% via only a 5 min incubation. Moreover, the isolated cells remained viable at 90.5 +/- 1.2%, and they could be directly used for culture, reverse transcription polymerase chain reaction (RT-PCR), and immunocytochemistry (ICC) identification. ICC identification and enumeration of the tumor cells in the same blood samples showed high sensitivity and good reproducibility. Furthermore, the IMNs were successfully applied to the isolation and detection of CTCs in cancer patient peripheral blood samples, and even one CTC in the whole blood sample was able to be detected, which suggested they would be a promising tool for CTC enrichment and detection.