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>>镀银金纳米星检测早期癌症生物标志物:新的光学感测平台可在患者组织直接检测基因组癌症生物标志物

A close-up view of a handful of nanostars used to create a new type of cancer diagnostic.  CREDIT Tuan Vo-Dinh, Duke University
A close-up view of a handful of nanostars used to create a new type of cancer diagnostic. CREDIT Tuan Vo-Dinh, Duke University

Abstract:
在杜克大学生物医学工程师已经设计用于同时检测从组织样品而不需要标记或靶扩增提取的RNA中的多个特定微RNA的存在的方法。该技术可用于识别癌症和其他疾病的早期生物标记物,而不需要精心,费时,昂贵的由当前技术所需的流程和专门的实验室设备。

镀银金纳米星发现早期癌症生物标志物:新的光学传感平台可以在患者的组织中直接检测基因组癌症生物标记

北卡罗来纳州达勒姆|发表于2020年7月24日

结果5月4日在该杂志分析网上出现了。

"The general research focus in my lab has been on the early detection of diseases in people before they even know they're sick," said Tuan Vo-Dinh, director of the Fitzpatrick Institute for Photonics and the R. Eugene and Susie E. Goodson Distinguished Professor of Biomedical Engineering at Duke. "And to do that, you need to be able to go upstream, at the genomic level, to look at biomarkers like microRNA."

微小RNA是短RNA分子结合到信使RNA,并从他们的交付指令到体内的蛋白质生产机器阻止他们。这可以有效沉默DNA的某些部分或调节基因表达,从而改变的某些生物学功能的行为。超过2000米的microRNA已经影响发育,分化,生长和代谢人类发现。

研究人员发现,ab学到更多的东西out these tiny genetic packages, many microRNAs have been linked to the misregulation of biological functions, resulting in diseases ranging from brain tumors to Alzheimer's. These discoveries have led to an increasing interest in using microRNAs as disease biomarkers and therapeutic targets. Due to the very small amounts of miRNAs present in bodily samples, traditional methods of studying them require genetic-amplification processes such as quantitative reverse transcription PCR (qRT-PCR) and RNA sequencing.

While these technologies perform admirably in well-equipped laboratories and research studies that can take months or years, they aren't as well-suited for fast diagnostic results at the clinic or out in the field. To try to bridge this gap in applicability, Vo-Dinh and his colleagues are turning to silver-plated gold nanostars.

“黄金纳米星有多个峰值,可以作为照明棒提高电磁波,这是粒子的形状的独特的功能作用,” VO-亭,谁也持有杜克化学教员聘任说。vwin徳赢官网“我们的微小纳米传感器,被称为‘逆分子的哨兵’,利用这种能力来创建多个微RNA的存在明确的信号优势。”

虽然名字很拗口,纳米传感器设计的基本想法是让一个标记分子,当靶RNA的特定拉伸认识,并找到了非常接近移动到明星的尖峰。当激光然后对触发的传感器照射的NANOSTAR尖端的避雷针效应导致所述标记分子以非常明亮地发光,信令靶RNA的捕获。

The researchers set this trigger by tethering a label molecule to one of the nanostar's points with a stretch of DNA. Although it's built to curl in on itself in a loop, the DNA is held open by an RNA "spacer" that is tailored to bind with the target microRNA being tested for. When that microRNA comes by, it sticks to and removes the spacer, allowing the DNA to curl in on itself in a loop and bring the label molecule in close contact with the nanostar.

下激光激发,该标签发射称为拉曼信号光,这通常是非常弱的。但纳米星的形状 - 和所引起的金纳米星和银涂层的单独反应的耦合效应 - 放大几百万倍拉曼信号,使它们更容易被检测到。

“标记分子的拉曼信号表现出非常具体的颜色,如光谱指纹,使检测到的当他们容易地彼此区分的尖锐峰,” VO-亭说。“因此,我们可以实际设计不同的传感器用于在纳米星不同的微小RNA,每个标记分子表现出各自特定的光谱指纹。而且由于该信号是如此之强,我们可以检测这些指纹彼此独立的每一个。”

在这项临床研究中,VO-亭和这支球队在杜克大学癌症研究所的凯瑟琳加曼,医学副教授,和他的同事合作,使用新的纳米传感器平台,以证明他们能够检测miR-21的,具有非常相关的特定微RNA食道癌的早期阶段,只是还有其他更复杂的国家的最先进的方法。在这种情况下,使用miR-21的单独的,就足以从癌症样本区分健康的组织样本。对于其他疾病,但是,它可能需要检测其他几个微RNA得到一个可靠的诊断,这就是为什么研究人员如此通过逆分子定点纳米生物传感器的普遍适用性兴奋。

“平时三四个基因生物标志物可能足以获得良好的诊断,这些类型的生物标志物可以明白无误地确定每种疾病,” VO-亭说。“这就是为什么我们的究竟有多强我们的纳米星,而无需费时目标扩增产生信号的鼓舞。我们的方法可以以组织病理学和PCR提供诊断替代方案,从而简化了癌症诊断测试的过程。”

For more than three years, Vo-Dinh has worked with his colleagues and Duke's Office of Licensing and Ventures to patent his nanostar-based biosensors. With that patent recently awarded, the researchers are excited to begin testing the limits of their technology's abilities and exploring technology transfer possibilities with the private sector.

"Following these encouraging results, we are now very excited to apply this technology to detect colon cancer directly from blood samples in a new NIH-funded project," said Vo-Dinh. "It's very challenging to detect early biomarkers of cancer directly in the blood before a tumor even forms, but we have high hopes."

###

This research was supported by the National Institutes of Health (1R21CA196426) and the National Science Foundation (1106401).

####

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联系方式:
Ken Kingery

919-660-8414

@DukeU

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Related Links

CITATION: "Plasmonic Nanobiosensors for Detection of MicroRNA Cancer Biomarkers in Clinical Samples," Bridget M. Crawford, Hsin-Neng Wang, Christina Stolarchuk, Richard J. von Furstenberg, Pietro Strobbia, Dadong Zhang, Xiaodi Qin, Kouros Owzar, Katherine S. Garman, Tuan Vo-Dinh. Analyst, May 4, 2020. DOI: 10.1039/D0AN00193G:

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