Multifunctional luminescent immuno-magnetic nanoparticles: toward fast, efficient, cell-friendly capture and recovery of circulating tumor cells.
Multifunctional luminescent immuno-magnetic nanoparticles: toward fast, efficient, cell-friendly capture and recovery of circulating tumor cells.
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DOI：
10.1039/c8tb02701c
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发表时间：
2019-01
期刊：
影响因子：
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通讯作者：
Xiaoxi Zhou;Bin Luo;Ke Kang;Shaohua Ma;Xiaohui Sun;Fang Lan;Qiangying Yi;Yao Wu
中科院分区：
文献类型：
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作者：
Xiaoxi Zhou;Bin Luo;Ke Kang;Shaohua Ma;Xiaohui Sun;Fang Lan;Qiangying Yi;Yao Wu
从患者血液中高效分离和回收有活力的循环肿瘤细胞（CTC）是解决当前CTC研究不足的困境的重要前提，并可促进个体化抗肿瘤治疗的发展。本文中，使用逐层（LbL）组装技术和刺激的细胞释放策略建立了具有发光标记的细胞友好的CTC分离和回收纳米平台。特别地，将抗上皮细胞粘附分子（抗EpCAM）抗体与含二硫键的接头一起引入，以进一步生物友好地回收CTC。通过简单的LbL组装方法将量子点沉积到快速磁响应的Fe 3 O 4纳米颗粒上，以真实的实时监测捕获和回收过程。所获得的PEG化免疫磁性纳米球（PIMNs）可以在2分钟内全部被磁性收集。仅在1-2分钟孵育后，可以从每mL具有5-200个CTC的血液样品中实现90%以上的捕获效率。在谷胱甘肽（GSH）处理15分钟后，几乎所有CTC表面上的PIMN都脱落，QD信号消失。传代后的CTC可直接用于培养（细胞存活率为98%），其侵袭性和迁移特性保持不变。此外，PIMNs成功地应用于分离癌症患者外周血样品中的CTC，平均每mL检测到8.6 ± 5.8个CTC。上述结果表明，PIMNs可以作为一个强大的纳米平台，用于CTC的筛选，分离和回收。
Highly efficient isolation and recovery of viable circulating tumor cells (CTCs) from the blood of patients is an important precondition to address the current dilemma of insufficient CTC studies, and can promote the development of individualized antitumor therapies. Herein, a cell-friendly CTC isolation and recovery nanoplatform with luminescent labelling was established using a layer-by-layer (LbL) assembly technique and a stimulated cellular-release strategy. In particular, the anti-epithelial cell adhesion molecule (anti-EpCAM) antibody was introduced with a disulfide bond-containing linker for further bio-friendly recovery of the CTCs. Quantum dots (QDs) were deposited onto fast magnet-responsive Fe3O4 nanoparticles through a facile LbL assembly method to monitor the capture and recovery process in real time. The obtained PEGlyated immuno-magnetic nanospheres (PIMNs) can all be magnetically collected within 2 min. Capture efficiencies above 90% can be achieved from blood samples with 5-200 CTCs per mL after only 1-2 min incubation. Nearly all PIMNs on the surface of the CTCs were detached after 15 min of glutathione (GSH) treatment with the disappearance of QD signals. Recovered CTCs could be directly used for culture (cell viability, ∼98%), and their invasiveness and migration characteristics remained unchanged. Furthermore, the PIMNs were successfully applied to isolate CTCs in cancer patients' peripheral blood samples, and an average of 8.6 ± 5.8 CTCs per mL was detected. The results above suggested that PIMNs may serve as a powerful nanoplatform for CTC screening, isolation and recovery.