Huang Shan, Yao Huiqin, Wang Wenjing, Zhang Jian-Rong, Zhu Jun-Jie
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China.
J Mater Chem B. 2018 Jul 28;6(28):4583-4591. doi: 10.1039/c8tb00801a. Epub 2018 Jun 4.
As an important biomarker for early cancer diagnosis and a valuable therapeutic target, the detection and monitoring of telomerase activity has attracted extensive attention. Herein, we constructed a novel fluorescent reporter to detect the intracellular telomerase activity based on guanine enhanced sliver nanoclusters (Ag NCs). In this system, a telomerase substrate (Ts) was designed to be extended by telomerase to give the repeat TTAGGG sequence as G-rich DNA, which was complementary to the nine base sequence to form a self-hairpin structure. The proximity of G-rich DNA to the as-prepared Ag NCs resulted in a 13-fold enhancement of fluorescence intensity due to the electron transfer from guanine to the Ag NCs. Therefore, the fluorescent probe could realize the detection of telomerase activity. Furthermore, the probe was successfully used to distinguish normal cells from cancer cells and to monitor the real time telomerase activity response upon treatment with an inhibiting model drug. This detection technique is simple, with excellent biocompatibility, inexpensive and expands the applications of the Ag NC probe.
作为早期癌症诊断的重要生物标志物和有价值的治疗靶点，端粒酶活性的检测与监测受到了广泛关注。在此，我们基于鸟嘌呤增强银纳米簇（Ag NCs）构建了一种新型荧光报告分子，用于检测细胞内端粒酶活性。在该系统中，设计了一种端粒酶底物（Ts），通过端粒酶进行延伸，生成重复的TTAGGG序列作为富含G的DNA，其与九碱基序列互补形成自发卡结构。由于鸟嘌呤向Ag NCs的电子转移，富含G的DNA与制备好的Ag NCs接近导致荧光强度增强了13倍。因此，该荧光探针能够实现端粒酶活性的检测。此外，该探针成功用于区分正常细胞和癌细胞，并监测用抑制性模型药物处理后的端粒酶活性实时响应。这种检测技术简单，具有优异的生物相容性，成本低廉，扩展了Ag NC探针的应用。
