Recent advances in nanozyme assisted miRNA biosensing for disease diagnosis.

MiRNAs have emerged as key biomarkers for early disease detection and therapeutic monitoring; yet, their ultrasensitive and specific detection confronts challenges due to low expression levels in biological fluids and high sequence homology, therefore it demands innovative sensing strategies. Enzyme mimicking nanostructures or nanozymes, enable manifold signal amplification and ultrasensitive analyte detection. In recent years, nanozymes, mainly oxidases and peroxidases, have been used as signal amplifiers in miRNA sensors due to their detectable catalytic products at low concentrations. Considering the increasing use of nanozymes in miRNA detection, this dedicated review presents the latest advancements in the field of miRNA diagnostics and unravels the contributions of nanozymes in miRNA sensing. This work highlights two major approaches commonly used for miRNA detection in sensors; (i) assisted through nucleic acid amplification, and (ii) amplification-free approaches. It then comprehensively underpins nanozymes as signal amplifier in both aforementioned strategies through diverse sensing modalities such as colorimetry, electrochemical, SERS, and chemiluminescent. It further presents the enhancement of sensitivity through integration of nanozymes with latest technologies like machine learning based approaches, CRISPR-Cas, or towards designing point of care sensors. Lastly, the review explores the challenges in translating nanozyme-derived miRNA sensing platforms to clinical settings.