Ultrasensitive biosensor for microRNA-155 using synergistically catalytic nanoprobe coupled with improved cascade strand displacement reaction

MicroRNAs, essential for gene expression and physiological regulation, are considered to be reliable biomarkers for the early diagnosis and treatment of cancers. Herein, a sensitive biosensor that uses a synergistically catalytic nanoprobe and improved toehold strand displacement reaction (TSDR) has been fabricated, and successfully applied to microRNA-155 (miR-155) detection. A nanoscale copper-based metal organic framework assembled by Pt nanoparticles and horseradish peroxidase (Cu-NMOF@PtNPs/HRP) served as a co-catalytic nanoprobe and was coupled with improved TSDR to achieve multiple amplifications. In the absence of miR-155, the tetrahedral DNA nanostructures (TDNs) immobilized on the gold electrode were independent of the TSDR system because of the binding of the shielding region of the locked probe (LP) with the template probe (TP). Instead, the target would initiate the TSDR system, leading to the conformational change of TDNs and hybridization of the nanoprobe. Cu-NMOF@PtNPs/HRP exhibited extraordinary catalytic property towards the hydroquinone-hydrogen peroxide system, demonstrating that the nanoprobe exerted a concerted effect on the electrochemical performance of the biosensor. Under optimal conditions, the cathodic current exhibited a logarithmic relation over 0.50-1.0 × 105fM miR-155, with a detection limit of 0.13 fM, indicating that the constructed biosensor has considerable potential in the field of clinical disease diagnostics for miR-155.