Novel nanosensors for rapid analysis of telomerase activity
Novel nanosensors for rapid analysis of telomerase activity
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DOI：
10.1158/0008-5472.can-03-2798
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发表时间：
2004-01-15
期刊：
影响因子：
11.2
通讯作者：
Weissleder, R
中科院分区：
文献类型：
--
作者：
Grimm, J;Perez, JM;Weissleder, R
在许多恶性肿瘤中发现端粒酶水平升高，这为治疗干预以及诊断或预后目的提供了一个有吸引力的靶点。在此我们描述了一种新型纳米传感器的使用，该传感器是为快速检测生物样本中的端粒酶活性而开发的。该技术利用磁性纳米粒子，当这些粒子与端粒酶合成的TTAGGG重复序列退火时，会改变其磁性状态，这一现象很容易被磁读取器检测到。我们在人类和小鼠的粗样本中测试了不同端粒酶抑制剂的功效，并表明端粒酶的磷酸化调节其活性。通过磁共振成像对该技术进行高通量适配，能够在几十分钟内以超高灵敏度处理数百个样本。总之，这些研究建立并验证了一种新颖且强大的快速检测端粒酶活性的工具，并为开发用于体内检测的类似磁性纳米粒子提供了理论依据。
Elevated telomerase levels are found in many malignancies, offering an attractive target for therapeutic intervention and diagnostic or prognostic purposes. Here we describe the use of a novel nanosensor developed for rapid screens of telomerase activity in biological samples. The technique utilizes magnetic nanoparticles that, on annealing with telomerase synthesized TTAGGG repeats, switch their magnet state, a phenomenon readily detectable by magnetic readers. We tested the efficacy of different telomerase inhibitors in crude human and murine samples and show that phosphorylation of telomerase regulates its activity. High-throughput adaptation of the technique by magnetic resonance imaging allowed processing of hundreds of samples within tens of minutes at ultrahigh sensitivities. Together, these studies establish and validate a novel and powerful tool for rapidly sensing telomerase activity and provide the rationale for developing analogous magnetic nanoparticles for in vivo sensing.