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基于 DNA 计算介导的 DNA zyme 平台的时空控制超灵敏分子成像。

Spatiotemporally Controlled Ultrasensitive Molecular Imaging Using a DNA Computation-Mediated DNAzyme Platform.

机构信息

Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, MOE; College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, P. R. China.

出版信息

Anal Chem. 2022 Oct 18;94(41):14467-14474. doi: 10.1021/acs.analchem.2c03532. Epub 2022 Oct 4.

Abstract

Programming ultrasensitive and stimuli-responsive DNAzyme-based probes that contain logic gate biocomputation hold great potential for precise molecular imaging. In this work, a DNA computation-mediated DNAzyme platform that can be activated by 808 nm NIR light and target -MYC was designed for spatiotemporally controlled ultrasensitive AND-gated molecular imaging. Particularly, the sensing and recognition function of the traditional DNAzyme platform was inhibited by introducing a blocking sequence containing a photo-cleavable linker (PC-linker) that can be indirectly cleaved by 808 nm NIR light and thus enables the AND-gated molecular imaging. According to the responses toward three designed SDz, nPC-SDz, and -SDz DNAzyme probes, the fluorescence recovery in diverse cell lines (MCF-7, HeLa, and L02) and inhibitor-treated cells was investigated to confirm the AND-gated sensing mechanism. It is worth noting that thanks to the strand displacement amplification and the ability of gold nanopyramids (Au NBPs) to enhance fluorescence, the fluorescence intensity increased by ∼7.9 times and the detection limit decreased by nearly 40.5 times. Moreover, false positive signals can be also excluded due to such AND-gated design. Furthermore, such a designed "AND-gate" sensing manner can also be applied to spatiotemporally controlled ultrasensitive in vivo molecular imaging, indicating its promising potential in precise biological molecular imaging.

摘要

设计了一种可被 808nm 近红外光激活并靶向-MYC 的基于 DNA 计算的 DNA 酶平台,用于时空控制的超灵敏 AND 门控分子成像。特别是,通过引入包含光裂解连接子(PC-连接子)的阻断序列,抑制了传统 DNA 酶平台的传感和识别功能,该连接子可被 808nm 近红外光间接裂解,从而实现了 AND 门控分子成像。根据对三种设计的 SDz、nPC-SDz 和 -SDz DNA 酶探针的响应,在不同细胞系(MCF-7、HeLa 和 L02)和抑制剂处理的细胞中研究了荧光恢复,以确认 AND 门控传感机制。值得注意的是,由于链置换扩增和金纳米金字塔(Au NBPs)增强荧光的能力,荧光强度增加了约 7.9 倍,检测限降低了近 40.5 倍。此外,由于这种 AND 门控设计,还可以排除假阳性信号。此外,这种设计的“AND 门”传感方式也可应用于时空控制的超灵敏体内分子成像,表明其在精确生物分子成像中具有广阔的应用前景。

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