MicroRNAs (miRNAs) play important roles in cell differentiation, proliferation, and apoptosis and have been recognized as valuable biomarkers for clinical disease diagnosis. Here, we adopt for the first time zeolitic imidazolate framework-8 (ZIF-8) as a nanocarrier to efficiently deliver a nucleic acid probe to living cells and develop a novel ratiometric fluorescence strategy based on DNAzyme for miRNA-21 imaging. A Cy5-labeled 8-17 DNAzyme strand and a Cy3-labeled substrate strand containing a segment complementary to the target miRNA-21 first form a duplex probe, and fluorescence resonance energy transfer (FRET) takes place. After adsorption on the ZIF-8 surface and cellular uptake, the probe/ZIF-8 nanocomplex degrades in acidic endosome and releases duplex probes and Zn²⁺, and the latter can act as an effective cofactor for 8-17 DNAzyme. The intracellular miRNA-21 hybridizes with the complementary segment of the substrate strand and results in dissociation from the DNAzyme–substrate duplex probe after DNAzyme cleaves the substrate into two fragments, accompanied by the change in the FRET signal. The proposed method has been applied to image miRNA-21 expression levels in MCF-7, HeLa, and L02 cells with high contrast and reliability. The fluctuation of miRNA-21 expression level induced by miRNA-21 mimic or inhibitor can also be monitored through the obvious imaging color change. Taken together, the proposed method provides a powerful tool for cancer diagnosis and miRNA-associated biological study.

中文翻译：

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纳米级沸石咪唑盐框架-8用于活细胞中微小RNA的比例荧光成像。

微小RNA（miRNA）在细胞分化，增殖和凋亡中起重要作用，并已被公认为是临床疾病诊断的有价值的生物标记。在这里，我们第一次采用沸石咪唑盐骨架8（ZIF-8）作为纳米载体，以有效地将核酸探针递送至活细胞，并开​​发基于DNAzyme的新型比例荧光方法用于miRNA-21成像。Cy5标记的8-17 DNAzyme链和Cy3标记的底物链（包含与目标miRNA-21互补的区段）首先形成双链探针，然后发生荧光共振能量转移（FRET）。在ZIF-8表面吸附并被细胞摄取后，探针/ ZIF-8纳米复合物在酸性内体中降解并释放出双链探针和Zn ²⁺，后者可以充当8-17 DNAzyme的有效辅助因子。细胞内miRNA-21与底物链的互补片段杂交，并在DNAzyme将底物切割成两个片段后伴随着FRET信号的改变，导致与DNAzyme-底物双链探针解离。拟议的方法已被应用于图像miRNA-21在MCF-7，HeLa和L02细胞中的表达水平，具有很高的对比度和可靠性。miRNA-21模拟物或抑制剂诱导的miRNA-21表达水平的波动也可以通过明显的成像颜色变化进行监测。综上所述，所提出的方法为癌症诊断和与miRNA相关的生物学研究提供了强大的工具。