Extracellular Vesicles as Mediators of Intercellular Communication: Implications for Drug Discovery and Targeted Therapies

Extracellular vesicles (EVs) are emerging as versatile mediators of intercellular communication and promising tools for drug discovery and targeted therapies. These lipid bilayer-bound nanovesicles facilitate the transfer of functional proteins, RNAs, lipids, and other biomolecules between cells, thereby influencing various physiological and pathological processes. This review outlines the molecular mechanisms governing EV biogenesis and cargo sorting, emphasizing the role of regulators, such as ubiquitin-like 3 (UBL3), in modulating protein packaging. We explored the critical involvement of EVs in various disease microenvironments, including cancer progression, neurodegeneration, and immune modulation. Their ability to cross biological barriers and deliver bio-active cargo renders them highly attractive for precise drug delivery systems, especially in neurological and oncological disorders. Moreover, this review highlights advances in engineering EVs for delivering RNA therapeutics, CRISPR-Cas systems, and targeted small molecules. The utility of EVs as diagnostic tools in liquid biopsies and their integration into personalized medicine and companion diagnostics were also discussed. Patient-derived EVs offer dynamic insights into disease state and enable real-time treatment stratification. Despite their potential, challenges such as scalable isolation, cargo heterogeneity, and regulatory ambiguity remain significant hurdles. We also reported novel pharmacological approaches targeting EV biogenesis, secretion, and uptake pathways, and considered UBL3 as a promising drug target for EV cargo modulation. Future directions include the standardization of EV analytics, scalable biomanufacturing, and classification of EV-based therapeutics under evolving regulatory frameworks. This review emphasizes the multifaceted roles of EVs and their transformative potential as therapeutic platforms and biomarker reservoirs in next-generation precision medicine.