Biocatalysis-mediated MOF-to-prussian blue transformation enabling sensitive detection of NSCLC-associated miRNAs with dual-readout signals

Sensitive and accurate miRNAs assay is critical for early diagnosis of non-small-cell lung carcinomas (NSCLC). Herein, we demonstrate a photothermal and electrochemical dual-readout assay method for miRNA detection based on a novel biocatalysis-mediated MOF-to-prussian blue (PB) transformation (BMMPT) strategy and the catalytic hairpin assembly (CHA) amplification strategy. It is found that the Fe2+-based MOF (MOF-Fe2+) can act as the Fe2+ source to react with K3[Fe(CN)6], leading to the in-situ formation of prussian blue (PB) on MOF-Fe2+. Due the inherent near-infrared (NIR) photothermal conversion ability and electrochemical signal of PB, the resulting PB@MOF-Fe2+ is employed to arouse temperature readout or electrochemical signal. The presence of target miRNA-21 triggers the CHA reaction on magnetic beads (MBs), resulting the capture of numerous glucose oxidase (GOx) tags on MBs. The GOx tags then catalyze the generation of H2O2 using glucose as substrate. The H2O2 is used to inhibit the MOF-to-PB transformation process by oxidizing Fe2+ into Fe3+, leading to the decrease in temperature and electrochemical readout aroused by PB@MOF-Fe2+. By this means, a signal-off assay mode with dual readout is established for miRNA-21. Under the optimal conditions, using temperature readout or electrochemical readout, miRNA-21 can be detected at concentrations as low as 0.3 fM and 0.32 fM, respectively. Moreover, the developed method is successfully applied to evaluate the expression level of miRNA-21 in serum of NSCLC patients. This work not only provides a practical tool for NSCLC diagnosis but also presents the new features of MOF materials as signal transduction tags.