Affinity-based nanostructured platforms for the selective pretreatment, enrichment and detection of miRNA biomarkers

MicroRNAs (miRNAs) are clinically relevant liquid-biopsy biomarkers, yet their reliable quantification is still limited by low abundance, matrix complexity, and frequent association with protective carriers such as Argonaute-2 and exosomes. This review focuses on affinity-based nanostructured platforms as superior tools for the selective pretreatment and enrichment of miRNAs, bridging the gap between raw clinical samples and high-performance analysis. We summarize key nanomaterial architectures, including functional nanoparticles, electrospun nanofibers, 2D nanomaterial platforms, and hybrid nanocomposites, together with surface functionalization strategies that enable the liberation of miRNAs from protein complexes and their subsequent sequence-specific capture. Emphasis is placed on how these enrichment workflows address target accessibility in protein-rich biofluids and mitigate matrix-induced interference. Beyond sample preparation, we evaluate the integration of these platforms with advanced detection modalities, including Surface-Enhanced Raman Spectroscopy (SERS) using inverse molecular sentinel (iMS) nanoprobes, enzyme-free hybridization chain reactions (HCR) and CRISPR/Cas-based assays. These innovative strategies circumvent the limitations of enzymatic amplification, offering high sensitivity and specificity. Finally, we address challenges in automation and standardization, highlighting the need for integrated enrichment-to-detection workflows that accelerate the translation of nanomaterial innovation and next-generation, point-of-care miRNA diagnostics.