DNA Amplifier-Functionalized Metal–Organic Frameworks for Multiplexed Detection and Imaging of Intracellular mRNA

DNA amplification is a useful technique for low-abundance biomarker detection and environmental monitoring because of its high signal-amplifying ability. However, intracellular application of DNA amplifiers remains challenging due to poor delivery efficiency and stability. Herein, we report an entropy-driven DNA amplifier-functionalized metal-organic framework (DNA amplifier-MOF) for the detection and imaging of multiple intracellular messenger RNAs (mRNAs). The DNA amplifier-MOF conjugate exhibits high cellular uptake, enhanced enzymatic stability, and good biocompatibility. Importantly, in the presence of phosphate ions, a surface-functionalized DNA amplifier can be released in cells with high efficiency, which facilitates the imaging of mRNA. This method is rapid and of high sensitivity/specificity, as validated in HepG2 and HL7702 cells for the imaging of TK1 and survivin mRNA, respectively. With further optimization, the strategy can become a powerful biotechnology tool for the detection of cancers at early stages and for elucidating biological processes.