Nanozyme‐Driven Next‐Generation miRNA Biosensing

ABSTRACT MicroRNAs (miRNAs) are small, noncoding RNA molecules nearly 22 nucleotides in length that contribute significantly to regulating gene expression. Their aberrant expression patterns are associated with disease progression, including cardiovascular and neurological disorders and cancer. However, the rapid detection of miRNAs remains challenging due to their low abundance, sequence similarity, and degradation. Conventional methods of detecting miRNAs, such as Northern blotting, microarray analysis, quantitative reverse transcription polymerase chain reaction (RT‐qPCR), and next‐generation sequencing (NGS), offer significant benefits for miRNA profiling, though they have drawbacks, including limited specificity, complex workflows, relatively high cost, and specialized equipment requirements. Advanced methodologies driven by nanotechnology, especially those that combine clustered regularly interspaced short palindromic repeats (CRISPR)/Cas approaches, provide revolutionary developments. Nanozymes enhance the stability and biocompatibility of catalytic amplification, while CRISPR technologies enable real‐time, multiplex, and ultrasensitive miRNA detection with accurate sequence recognition. The rapidly expanding field encompasses diverse nanozyme architectures, recognition mechanisms, amplification strategies, and signal‐transduction platforms, providing a broad basis for critically assessing advances, limitations, and emerging opportunities in nanozyme‐enabled miRNA biosensing. Nanozyme‐enabled miRNA detection has evolved across diverse sensing platforms, such as colorimetric and optical assays, sophisticated photoelectrochemical (PEC) and electrochemiluminescence (ECL) biosensors, and portable and paper‐based diagnostic technologies. The convergence of nanozyme catalysis, CRISPR‐based recognition, and advanced sensing strategies holds promise for sensitive, selective, and portable miRNA diagnostics.