Lim Jiyun, Choi Mihye, Lee HyungJae, Han Ji-Youn, Cho Youngnam
Biomarker Branch, National Cancer Center, Goyang, South Korea.
Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, Goyang, South Korea.
Front Chem. 2019 Jan 15;6:664. doi: 10.3389/fchem.2018.00664. eCollection 2018.
Circulating tumor-specific markers are crucial to understand the molecular and cellular processes underlying cancer, and to develop therapeutic strategies for the treatment of the disease in clinical applications. Many approaches to isolate and analyze these markers have been reported. Here, we propose a straightforward method for highly efficient capture and release of exosomes and circulating tumor cells (CTCs) in a single platform with well-ordered three-dimensional (3D) architecture that is constructed using a simple electrochemical method. Conductive polypyrrole nanowires (Ppy NWs) are conjugated with monoclonal antibodies that specifically recognize marker proteins on the surface of exosomes or CTCs. In response to electrical- or glutathione (GSH)-mediated stimulation, the captured exosomes or cells can be finely controlled for retrieval from the NW platform. A surface having nano-topographic structures allows the specific recognition and capture of small-sized exosome-like vesicles (30-100 nm) by promoting topographical interactions, while physically blocking larger vesicles (i.e., microvesicles, 100-1,000 nm). In addition, vertically aligned features greatly improve cell capture efficiency after modification with desired high-binding affinity biomolecules. Notably, exosomes and CTCs can be sequentially isolated from cancer patients' blood samples using a single NW platform via modulating electrochemical and chemical cues, which clearly exhibits great potential for the diagnosis of various cancer types and for downstream analysis due to its facile, effective, and low-cost performance.
循环肿瘤特异性标志物对于理解癌症潜在的分子和细胞过程以及在临床应用中开发治疗该疾病的策略至关重要。已经报道了许多分离和分析这些标志物的方法。在此，我们提出了一种直接的方法，用于在一个具有有序三维（3D）结构的单一平台上高效捕获和释放外泌体和循环肿瘤细胞（CTC），该平台是使用简单的电化学方法构建的。导电聚吡咯纳米线（Ppy NWs）与单克隆抗体偶联，这些单克隆抗体特异性识别外泌体或CTC表面的标志物蛋白。响应电或谷胱甘肽（GSH）介导的刺激，可以精确控制从NW平台中回收捕获的外泌体或细胞。具有纳米拓扑结构的表面通过促进拓扑相互作用允许特异性识别和捕获小尺寸的外泌体样囊泡（30 - 100 nm），同时物理阻挡较大的囊泡（即微囊泡，100 - 1000 nm）。此外，垂直排列的特征在用具有所需高结合亲和力的生物分子修饰后大大提高了细胞捕获效率。值得注意的是，通过调节电化学和化学线索，可以使用单个NW平台从癌症患者的血液样本中顺序分离外泌体和CTC，由于其简便、有效和低成本的性能，这在各种癌症类型的诊断和下游分析中显然具有巨大潜力。
