Extracellular vesicles in molecular crosstalk and disease pathogenesis: a comprehensive review on mechanisms and...

Extracellular vesicles (EVs) have emerged as central regulators of molecular communication between cells, tissues, and organs, which functioning as active conveyors of bioactive proteins, lipids, and coding and non-coding nucleic acids. EVs develop complex crosstalk networks that influence physiological homeostasis and accelerate disease development, as opposed to being passive byproducts of cellular turnover. This comprehensive review synthesizes current understanding of EV biogenesis, cargo selection, and functional heterogeneity, with a particular focus on how EV-mediated signaling rewires cellular behavior in pathological contexts. We integrate evidence across cancer, cardiovascular and neurodegenerative disorders, inflammatory and infectious diseases to highlight conserved and disease-specific mechanisms through which EVs regulate immune modulation, metabolic coordination, tissue remodeling, and host-pathogen interactions. The diagnostic and prognostic value of EVs as liquid biopsy platforms is critically examined, emphasizing their capacity to reflect dynamic communication states within diseased microenvironments. In parallel, emerging therapeutic strategies leveraging native and engineered EVs, as well as approaches aimed at disrupting pathogenic EV signaling through "crosstalk blockade," are discussed. Finally, key technical, biological, and translational challenges including EV heterogeneity, standardization, and clinical scalability are outlined, and future research priorities are proposed. Collectively, this review positions EVs as unifying mediators of molecular crosstalk and underscores their growing potential as diagnostic and therapeutic tools across diverse disease landscapes.