Metal-organic frameworks-assisted nonenzymatic cascade amplification multiplexed strategy for sensing acute myocardial infarction related microRNAs

Amplification strategies for multiple microRNAs (miRNAs) detection are pivotal for acute myocardial infarction (AMI). Herein, we rationally developed a metal-organic frameworks-assisted nonenzymatic cascade amplification strategy for simultaneous quantification of three AMI-related miRNAs (miR-21, miR-499 and miR-133a). The fluorescence of the elaborately designed DNA molecular beacons with the respective modification of FAM, TAMRA and Cy5 in the terminal was quenched by a metal-organic framework named Fe-MIL-88. When targets miRNA appeared, they hybridized with the corresponding DNA molecular beacons, and the catalyzed hairpin assembly (CHA) reaction would be triggered, producing "Y" shaped three-branched duplex nanostructure with the targets released, and initiating subsequent another cycle. The "Y" shaped nanostructures could not be adsorbed onto the surface of Fe-MIL-88 due to the weaker affinity between Fe-MIL-88 and "Y" shaped nanostructures. Therefore, the fluorescence of "Y" shaped nanostructures could not be quenched by Fe-MIL-88. In this way, three AMI-related miRNAs were simultaneously detected in the respective ranges of 0.05-30 nM, 0.08-30 nM and 0.1-20 nM with respective limits of detection down to 13, 25 and 40 pM. Furthermore, the method was successfully employed to determine three AMI-related miRNAs in human serum. The strategy offered great opportunity for ultrasensitive detecting multiple AMI-related miRNAs and substantially improving the accuracy of clinical early AMI diagnosis.