Highly Catalytic FeS 2 @CoS 2 Core/Shell Nanocubes for Ultrasensitive Electrochemical Assay of Microphthalmia-Associated Transcription Factor via Nucleic Acid Signal Amplification Cascades

Dysregulation expression of microphthalmia-associated transcription factor (MITF), a principal melanocyte controller, has been closely linked to melanin-associated disorders, and developing highly sensitive MITF detection methods is therefore imperative for early diagnosis and prognosis monitoring of melanoma-associated symptoms. This work describes an ultrasensitive electrochemical MITF biosensor on the basis of highly catalytic FeS₂@CoS₂ core/shell nanocubes and target recycling/bipedal DNA walker signal amplification cascades. The FeS₂@CoS₂ nanocubes are prepared with the one-step simple hydrothermal means, followed by their modification on the electrode, electrodeposition of AuNPs, and immobilization of DNA capture probes to prepare the sensing interface. Target MITF molecules bind and protect the dsDNA recognition duplexes from digestion by exonuclease III (Exo III) to trigger subsequent target recycling/bipedal DNA walker reaction cascades. This leads to confining a lot of ferrocene (Fc)-modified DNAs to the electrode sensing surface. FeS₂@CoS₂-mediated catalytic oxidation of Fc thus generates significantly amplified current signals, achieving MITF detection across 0.5 ∼ 1000 pM with the remarkable 0.12 pM detection limit. Moreover, such a biosensor shows excellent selectivity and can realize trace MITF detection in cancer cell nuclear extracts, demonstrating its potential as a universal platform for trace transcription factor detection.