Targeting Redox Signaling Through Exosomal MicroRNA: Insights into Tumor Microenvironment and Precision Oncology.

Reactive oxygen species (ROS) play a dual role in cancer progression, acting as both signaling molecules and drivers of oxidative damage. Emerging evidence highlights the intricate interplay between ROS, microRNAs (miRNAs), and exosomes within the tumor microenvironment (TME), forming a regulatory axis that modulates immune responses, angiogenesis, and therapeutic resistance. In particular, oxidative stress not only stimulates exosome biogenesis but also influences the selective packaging of redox-sensitive miRNAs (miR-21, miR-155, and miR-210) via RNA-binding proteins such as hnRNPA2B1 and SYNCRIP. These miRNAs, delivered through exosomes, alter gene expression in recipient cells and promote tumor-supportive phenotypes such as M2 macrophage polarization, CD8 T-cell suppression, and endothelial remodeling. This review systematically explores how this ROS-miRNA-exosome axis orchestrates communication across immune and stromal cell populations under hypoxic and inflammatory conditions. Particular emphasis is placed on the role of NADPH oxidases, hypoxia-inducible factors, and autophagy-related mechanisms in regulating exosomal output. In addition, we analyze the therapeutic relevance of natural products and herbal compounds-such as curcumin, resveratrol, and ginsenosides-which have demonstrated promising capabilities to modulate ROS levels, miRNA expression, and exosome dynamics. We further discuss the clinical potential of leveraging this axis for cancer therapy, including strategies involving mesenchymal stem cell-derived exosomes, ferroptosis regulation, and miRNA-based immune modulation. Incorporating insights from spatial transcriptomics and single-cell analysis, this review provides a mechanistic foundation for the development of exosome-centered, redox-modulating therapeutics. Ultimately, this work aims to guide future research and drug discovery efforts toward integrating herbal medicine and redox biology in the fight against cancer.