A novel cascade catalytic electrochemical biosensor based on bifunctional Mn3O4@AuNPs with self-supplied O2 property and glucose oxidase-like activity for ultrasensitive detection of microRNA

Herein, a bifunctional nanomaterial Mn3O4@AuNPs with self-supplied oxygen (O2) property and glucose oxidase-like activity was exploited to construct a novel cascade catalytic electrochemical biosensor for ultrasensitive detection of microRNA-499 (miRNA-499). Impressively, compared with the traditional AuNPs nanozyme with single glucose oxidase-like activity, the Mn3O4@AuNPs could not only act as a glucose oxidative mimetic enzyme to catalyze the oxidation of glucose to gluconic acid and the reduction of dissolved O2 to low concentration of hydrogen peroxide (H2O2) to obtain a electrochemical signal in the presence of hemin/G-quadruplex DNAzyme with peroxidase-like activity, but also electrocatalyze water splitting to obtain abundant dissolved O2 to further assist in the production of high concentration of H2O2 for a significantly improved electrochemical response. Meanwhile, with the aid of the target-induced dual Mg2+-assisted DNAzyme cleavage recycling amplification for the increasement of target miRNA-499 conversion efficiency, the proposed electrochemical biosensor achieved the ultrasensitive detection of miRNA-499 with a detection limit as low as 6.2 aM. As a result, this strategy might provide a potential method to upgrade the catalytic efficiency of mimic enzyme cascade reaction with eventual applications in bioanalysis and disease diagnosis.