Exosomal cargo sorting: mechanisms, functions, and therapeutic implications

Exosomal cargo is selectively packaged through highly regulated sorting pathways, enabling exosomes to exert distinct biological functions in diverse physiological and pathological contexts. Cellular states and environmental cues can shape these sorting processes, thereby influencing exosomal composition and function. Consequently, exosomes play critical roles in tumor progression, immune regulation, cardiovascular diseases, and neurodegenerative diseases, while emerging evidence also implicates them in mitochondria-related intercellular communication. This article outlines the regulatory mechanisms of exosome secretion and systematically summarizes the molecular pathways governing lipid, protein, and nucleic acid sorting. It further discusses how these mechanisms shape exosomal function and highlight their emerging applications in exosome engineering and therapeutic development. Cargo sorting, functional heterogeneity, and therapeutic strategies of exosomes. Exosome biogenesis proceeds via endosomal maturation into MVBs, where lipids, proteins, and nucleic acids are selectively sorted into ILVs through coordinated ESCRT-dependent and -independent pathways. Distinct cargo-sorting pathways generate exosomes with diverse molecular compositions, thereby shaping their functional heterogeneity in immune regulation, tumor progression, cardiovascular diseases, and neurodegenerative disorders. Understanding these sorting mechanisms also provides a conceptual framework for developing sorting-based therapeutic strategies and engineering exosomes with enhanced cargo sorting and targeting capabilities for precision medicine