Recent advances on miRNAs in extracellular vesicles: Molecular mechanisms, detection methods, and clinical...

Extracellular vesicle-derived miRNAs (EV-miRNAs) have emerged as pivotal liquid biopsy biomarkers due to their biogenesis-driven selective enrichment, exceptional stability within lipid bilayers, and essential regulatory roles in various diseases. This review provides a systematic and critical evaluation of the field by integrating molecular mechanisms, high-performance sensing technologies, and clinical translation progress, underscoring the necessity of accurate EV-miRNA quantification for disease diagnosis, treatment, and prognosis monitoring. Various emerging sensing technologies have been developed to enhance detection sensitivity and specificity, such as enzyme-based amplification strategies, membrane fusion-mediated approaches, nanomaterial-assisted signal conversion techniques, and integrated microfluidic platforms. Furthermore, the review summarises representative clinical advances in using EV-miRNAs for the diagnosis and monitoring of cancers, neurodegenerative disorders, and metabolic diseases. Significant emphasis is also placed on addressing analytical limitations, with the integration of AI-driven multi-omics models highlighted as a strategic frontier for enhancing clinical utility. This comprehensive synthesis establishes a robust theoretical and technical foundation for advancing EV-miRNA research from laboratory validation toward high-precision clinical translation.