Metal-organic frameworks-assisted nonenzymatic cascade amplification multiplexed strategy for sensing acute...

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.