DNA-functionalized metal-organic framework ratiometric nanoprobe for MicroRNA detection and imaging in live cells

MicroRNAs are short noncoding regulatory RNAs that are increasingly used as disease biomarkers. Rapid, sensitive, and quantitative microRNAs detection methods with high specificity are imperative. Here, we for the first time developed a DNA-functionalized metal-organic framework (MOF)-based ratiometric fluorescent probe using the interaction between Thiazole Orange (TO) dye and Rhodamine B(RhB) dye molecules, and achieved sensitive detection and imaging of miRNA-21 in living cells. Among them, DNA was successfully conjugated with MOF through the Zr-O-P bond in a single step with high efficiency. Based on this ratiometric fluorescent probe, picomolar limit detection (57 pM) for miRNA-21 can be obtained without signal amplification. After penetration into the cell, intracellular miRNA-21 can also be imaged by strand-displacement reaction, even distinguishing cancer cells from normal cells was achieved. This work paves the way for the development of DNA-functionalized MOF for intracellular molecules analysis and is of great significance for the early disease diagnosis.