Cell-SELEX-based selection of aptamers that recognize distinct targets on metastatic colorectal cancer cells
Cell-SELEX-based selection of aptamers that recognize distinct targets on metastatic colorectal cancer cells
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基于 Cell-SELEX 的适体选择可识别转移性结直肠癌细胞的不同靶标
DOI：
10.1016/j.biomaterials.2014.04.112
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发表时间：
2014-08-01
期刊：
影响因子：
14
通讯作者：
Fang, Jin
中科院分区：
文献类型：
--
作者：
Li, Wan-Ming;Bing, Tao;Fang, Jin
针对转移相关分子靶点的诊断/治疗策略的开发对于提高癌症患者的生存率至关重要。 Subtractive Cell-SELEX 分别使用高度转移性结直肠癌 (CRC) LoVo 细胞和非转移性 HCT-8 细胞作为靶细胞和阴性细胞进行，以选择转移特异性适体。该过程产生了七个适体，它们与靶细胞表现出高度特异性的结合，K(d)s 在纳摩尔范围内。根据各个细胞表面靶标不同的化学/生物学特性，对适配体进行单独功能化：受体靶向适配体W14用作阿霉素的载体，从而将药物特异性递送至靶细胞并显着降低其对非靶细胞的细胞毒性，非受体结合适配体W3用作分子探针 与量子点结合，用于转移性癌细胞系、自发性肺转移小鼠组织和转移性结直肠癌患者组织的靶向成像。此外，由于这些适体缺乏可检测到的相互结合干扰，因此可以组合使用。该研究表明，通过单次 Cell-SELEX 选择可以获得一组识别靶分子不同特征的适体，并且所选适体可以针对特定应用进行单独功能化和/或组合使用。 (C) 2014 Elsevier Ltd. 保留所有权利。
The development of diagnostic/therapeutic strategies against metastasis-related molecular targets is critical for improving the survival rate of cancer patients. Subtractive Cell-SELEX was performed using highly metastatic colorectal cancer (CRC) LoVo cells and non-metastatic HCT-8 cells as the target and negative cells, respectively, for the selection of metastatic-specific aptamers. This process generated seven aptamers that displayed highly specific binding to the target cells with K(d)s in the nanomolar range. Based on the distinct chemical/biological properties of their individual cell surface targets, the aptamers were separately functionalized: the receptor-targeting aptamer W14 was used as a carrier for doxorubicin, resulting in the specific delivery of the drug to the target cells and a significant reduction of its cytotoxicity to non-target cells, and the non-receptor-binding aptamer W3 was used as a molecular probe conjugated to quantum dots for the targeted imaging of metastatic cancer cell lines, spontaneous lung metastasis murine tissue, and metastatic CRC patient tissues. In addition, these aptamers can be used in combination due to their lack of detectable mutual-binding interference. The study demonstrates that a panel of aptamers that recognize distinct features of target molecules can be obtained through single Cell-SELEX selection, and the selected aptamers may be individually functionalized for specific applications and/or utilized in combination. (C) 2014 Elsevier Ltd. All rights reserved.