MicroRNA regulation by selenium nanoparticles: Mechanistic insights and translational perspectives in human disease

Selenium nanoparticles (SeNPs) have emerged as physicochemically tunable nanoplatforms at the intersection of redox biology and post-transcriptional gene regulation. This review provides a systems-level synthesis of current evidence linking SeNPs to microRNA (miRNA) modulation across cancer, inflammatory, metabolic, and degenerative disorders. A hybrid bibliometric-narrative strategy integrating Scopus, Web of Science, and PubMed initially identified 53 records, of which five met all inclusion criteria and were retained for mechanistic analysis of SeNP-mediated miRNA modulation. Recent studies predominantly employ green and biologically mediated synthesis routes, yielding biocompatible SeNPs with tunable physicochemical properties that determine cellular uptake, redox activity, and gene-regulatory engagement. Mechanistically, current evidence supports the working hypothesis that SeNPs influence redox-sensitive pathways-including Keap1-Nrf2, NF-κB, and p53/SIRT1-to potentially reshape miRNA networks central to oxidative stress, apoptosis, inflammation, and metabolic homeostasis. Key miRNA nodes modulated by SeNPs include miR-16, miR-20b, miR-21, miR-155, and members of the miR-200 family. Functionally, SeNP platforms upregulate tumor-suppressive miRNAs while attenuating oncogenic or pro-inflammatory counterparts, resulting in apoptosis induction, anti-metastatic signaling, mitochondrial restoration, immune modulation, and tissue-regenerative effects in preclinical models. Surface functionalization with polymers, peptides, or aptamers enhances targeting precision and supports integration with biosensing technologies such as surface-enhanced Raman spectroscopy and electrochemical platforms for miRNA detection. Despite promising preclinical evidence, translation remains constrained by synthesis variability, selenium's narrow therapeutic index, incomplete pharmacokinetic-pharmacodynamic mapping, and regulatory ambiguity. Advancing SeNP-miRNA therapeutics will require standardized green manufacturing, quality-by-design frameworks, and multi-omics-guided biomarker integration. Collectively, SeNP-mediated miRNA modulation represents a mechanistically grounded and adaptable platform for precision nanomedicine with emerging theranostic potential.