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基于生物标志物的 DNA 功能化胶体在细胞中的程序化同步组装与拆卸。

Biomarker-Driven DNA-Functionalized Colloidal Programmed Simultaneous Assembly and Disassembly in Cells.

机构信息

Shandong Province Key Laboratory of Detection Technology for Tumor Makers, College of Chemistry and Chemical Engineering, Linyi University, Linyi 276000, P. R. China.

Biomedical Science College, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250000, P. R. China.

出版信息

Anal Chem. 2024 Apr 30;96(17):6609-6617. doi: 10.1021/acs.analchem.3c05765. Epub 2024 Apr 19.

DOI:10.1021/acs.analchem.3c05765
PMID:38639728
Abstract

Complex structures and devices, both natural and artificial, can often undergo assembly and disassembly. Assembly and disassembly allow multiple stimuli to initiate, for example, the assembly and disassembly of primary cilia under the control of E3 ubiquitin ligases and deubiquitinases. Although biology relies on such schemes, they are rarely available in materials science. Here, we demonstrate a DNA-functionalized colloidal Au response to endogenous biomarkers to trigger simultaneous assembly and disassembly techniques. Colloidal Au is initially inert because the starting DNA strands are paired and prehybridized. TK1 mRNA competes to bind one of the paired strands and release its complement. The released complement binds to the next colloidal Au to initiate assembly, and APE1 can shear the colloidal Au assembly binding site to initiate disassembly. Our strategy provides temporal and spatial logic control during colloidal Au assembly and disassembly, and this simultaneous assembly and disassembly process can be used for sequential detection and cellular imaging of two biomarkers, effectively reducing signal false-positive results and shortening detection time. This work highlights biomarker-controlled colloidal Au simultaneous assembly and disassembly in ways that are simple and versatile, with the potential to enrich the application scope of DNA nanotechnology and provide an idea for the application of precision medicine testing.

摘要

复杂的结构和设备,无论是天然的还是人工的,通常都可以进行组装和拆卸。组装和拆卸允许多种刺激物引发,例如,在 E3 泛素连接酶和去泛素酶的控制下,初级纤毛的组装和拆卸。尽管生物学依赖于这样的方案,但它们在材料科学中很少见。在这里,我们展示了一种 DNA 功能化胶体 Au 对内源性生物标志物的响应,以触发同时组装和拆卸技术。胶体 Au 最初是惰性的,因为起始 DNA 链是配对的并且预杂交的。TK1 mRNA 竞争结合其中一条配对链并释放其互补链。释放的互补链与下一个胶体 Au 结合以启动组装,APE1 可以剪切胶体 Au 组装结合位点以启动拆卸。我们的策略在胶体 Au 的组装和拆卸过程中提供了时间和空间逻辑控制,并且这种同时的组装和拆卸过程可用于两种生物标志物的顺序检测和细胞成像,有效降低了信号假阳性结果并缩短了检测时间。这项工作突出了生物标志物控制的胶体 Au 的简单和通用的同时组装和拆卸方式,有可能丰富 DNA 纳米技术的应用范围,并为精准医学检测的应用提供了一个思路。

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Anal Chem. 2024 Apr 30;96(17):6609-6617. doi: 10.1021/acs.analchem.3c05765. Epub 2024 Apr 19.
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