Evolution of DNA aptamers for malignant brain tumor gliosarcoma cell recognition and clinical tissue imaging

Evolution of DNA aptamers for malignant brain tumor gliosarcoma cell recognition and clinical tissue imaging
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用于恶性脑肿瘤胶质肉瘤细胞识别和临床组织成像的DNA适体的进化

DOI:
10.1016/j.bios.2016.01.031
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发表时间:
2016
影响因子:
12.6
通讯作者:
Yang Chaoyong James
Yang Chaoyong James
中科院分区:
工程技术1区
文献类型:
--
作者:
Wu Qiaoyi;Wu Liang;Wang Yuzhe;Zhu Zhi;Song Yanling;Tan Yuyu;Wang Xing-Fu;Li Jiuxing;Kang Dezhi;Yang Chaoyong James

文献摘要

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胶质肉瘤是多形性胶质母细胞瘤(GBM)的一种变体,是一种高度侵袭性的恶性肿瘤。不幸的是,这种疾病的特点仍然是预后不良,无论现代治疗。寻找胶质肉瘤特异性分子探针对肿瘤的早期诊断和治疗具有重要意义。本研究利用cell-SELEX技术筛选出一组对胶质肉瘤细胞K308具有高亲和力和选择性的DNA适体。这些适体对胶质肉瘤细胞的解离常数均在纳摩尔范围内,其中WQY-9具有最高的亲和力和良好的选择性。此外,截短的适体序列WQY-9-B显示出与适体WQY-9相似的识别能力。此外,发现WQY-9-B能够在37 °C下选择性结合并内化到靶癌细胞的细胞质中。更重要的是,与随机序列相比,适体WQY-9-B对临床胶质肉瘤样品的组织切片显示出优异的识别率(73.3%)。这些数据表明,适体WQY-9-B具有良好的潜力,作为一个有效的分子探针诊断胶质肉瘤。
Gliosarcoma, a variant of glioblastoma multiforme (GBM), is a highly invasive malignant tumor. Unfortunately, this disease still marked by poor prognosis regardless of modern treatments. It is of great significance to discover specific molecular probes targeting gliosarcoma for early cancer diagnosis and therapy. Herein, we have selected a group of DNA aptamers with high affinity and selectivity against gliosarcoma cells K308 using cell-SELEX. All the dissociation constants of these aptamers against gliosarcoma cells were in the nanomolar range and aptamer WQY-9 has the highest affinity and good selectivity among them. Furthermore, truncated aptamer sequence, WQY-9-B, shows similar recognition ability to aptamer WQY-9. In addition, WQY-9-B was found to be able to bind selectively and internalize into cytoplasm of target cancer cell at 37 °C. More importantly, compared to a random sequence, aptamer WQY-9-B showed excellent recognition rate (73.3%) for tissue sections of clinical gliosarcoma samples. These data suggests that aptamer WQY-9-B has excellent potential as an effective molecular probe for gliosarcoma diagnosis.