Artificial Antibody with Site-Enhanced Multivalent Aptamers for Specific Capture of Circulating Tumor Cells
Artificial Antibody with Site-Enhanced Multivalent Aptamers for Specific Capture of Circulating Tumor Cells
复制标题
具有位点增强多价适体的人工抗体，用于特异性捕获循环肿瘤细胞
DOI：
10.1021/acs.analchem.8b05259
复制
发表时间：
2019
影响因子：
7.4
通讯作者：
Zhang Yukui
中科院分区：
文献类型：
--
作者：
Liu Lukuan;Yang Kaiguang;Gao Hang;Li Xiao;Chen Yuanbo;Zhang Lihua;Peng Xiaojun;Zhang Yukui
从血液中分离循环肿瘤细胞（CTC）具有诊断癌症和发现治疗靶点的巨大潜力。本文报道了一种新型的人工抗体--细胞印迹适体水凝胶（APT-CIH），用于特异性捕获CTC。细胞印迹位点不仅可以用于识别靶细胞，还可以作为组装适体的有效支架，提高捕获效率和选择性。由于适体与靶细胞之间的构象识别和多价相互作用的协同效应，APT-CIH对SMMC-7721细胞表现出较高的捕获效率和选择性。在1000倍白血病Jurkat细胞共存时，APT-CIH对靶细胞的富集因子可达21.6 ± 3.1，而仅依靠细胞印迹或适体亲和力的富集因子分别为8.1 ± 5.0和10.1 ± 1.3。当1 mL血液中加入1000个SMMC-7721细胞时，捕获效率可达58.2% ± 10.9%。此外，92%的捕获细胞可以被释放，有利于开展进一步的生物学和临床研究的CTC。这些结果表明APT-CIH在CTC分析中具有很大的潜力。
Isolation of circulating tumor cells (CTCs) from blood holds great potential to diagnose cancers and discover therapeutic targets. Herein, we reported a novel kind of artificial antibody, the cell-imprinted hydrogel with site-directed modification of aptamers (APT-CIH) to achieve the specific capture of CTCs. Cell-imprinted sites not only could be used to recognize target cells but also could be used as efficient scaffolds for assembling aptamers to enhance the capture efficiency and selectivity. Due to the synergistic effect of conformation recognition and multivalent interaction between the aptamers and target cells, APT-CIH showed high capture efficiency and selectivity to SMMC-7721 cells. In the coexistence of the 1000 times leukemia Jurkat cells, the enrichment factor of APT-CIH could reach as high as 21.6 ± 3.1 toward target cells, while that relied only on cell imprinting or aptamer affinity was 8.1 ± 5.0 or 10.1 ± 1.3, respectively. Furthermore, the capture efficiency could reach 58.2% ± 10.9% with 1000 SMMC-7721 cells spiked in 1 mL of blood. Moreover, 92% of the captured cells could be released, beneficial to carry out further biological and clinical study of CTCs. These results demonstrated that APT-CIH might have great potential in CTCs analysis.