Ultrasensitive Telomerase Activity Detection in Circulating Tumor Cells Based on DNA Metallization and Sharp Solid‐State Electrochemical Techniques
Ultrasensitive Telomerase Activity Detection in Circulating Tumor Cells Based on DNA Metallization and Sharp Solid‐State Electrochemical Techniques
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DOI：
10.1002/adfm.201303818
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发表时间：
2014-05
影响因子：
19
通讯作者：
Li Wu;Jiasi Wang;Jinsong Ren;Xiaogang Qu
中科院分区：
文献类型：
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作者：
Li Wu;Jiasi Wang;Jinsong Ren;Xiaogang Qu
循环肿瘤细胞（CTC）定量被认为是一种“液体活检”，对于评估癌症扩散、预测患者预后以及评估治疗性治疗具有重要意义，代表了侵入性活检和后续蛋白质组学和功能遗传分析的可靠潜在替代方案。与目前癌症诊断的金标准活检相比，血液检查的一个重要特征是它是安全的，可以在疾病期间的许多时间点进行，允许开发适当的治疗修改并可能改善患者的生活质量。在这项工作中，提出了一种超灵敏的电化学端粒酶活性传感策略，该策略利用DNA模板沉积的银纳米颗粒作为电活性标记物，通过高度尖锐的固态Ag/AgCl反应与DNA核酸外切酶III辅助的背景电流抑制。这种纳米颗粒介导的信号放大导致检测限显著降低，这优于绝大多数报道的方法，并实现了与传统端粒重复序列扩增方案（TRAP）相当的灵敏度。这项工作可能为通过非侵入性常规血液检测检测CTC中的端粒酶活性铺平了一条新的无PCR途径，用于癌症的即时诊断和个性化治疗。
Being considered a “liquid biopsy”, circulating tumor cell (CTC) quantification is of great interest for evaluating cancer dissemination, predicting patient prognosis, and also for the evaluation of therapeutic treatments, representing a reliable potential alternative to invasive biopsies and subsequent proteomic and functional genetic analysis. Compared to a biopsy, the gold standard of current cancer diagnosis, an important characteristic of a blood test is that it is safe and can be performed at many points during the disease, allowing the development of appropriate therapy modifications and potentially improving patient's quality of life. In this work, an ultrasensitive electrochemical telomerase activity‐sensing strategy is presented that utilizes DNA‐templated deposition of silver nanoparticles as electroactive labels through a highly sharp solid‐state Ag/AgCl reaction with DNA exonuclease III‐assisted background current suppression. This nanoparticle‐mediated signal amplification resulted in significantly decreased detection limit, which is better than the vast majority of reported methods and achieves a sensitivity comparable to the conventional telomeric repeat amplification protocol (TRAP). This work may pave a new PCR‐free way for the detection of telomerase activity in CTCs via a noninvasive routine blood test for point‐of‐care diagnosis and individualized treatment of cancer.