Engineering exosomes for liver disease: a new insight in regenerative medicine and drug delivery

Exosomes, nanoscale extracellular vesicles derived from endosomes, have emerged as crucial mediators of intercellular communication, significantly influencing physiological balance and disease development. Their biogenesis occurs via two different pathways-ESCRT-dependent and ESCRT-independent mechanisms-that regulate the selective packing of lipids, proteins, and nucleic acids. This review offers a mechanistic understanding of exosome production, cargo sorting, and secretion, highlighting their dynamic regulation in response to cellular stress conditions. Exosomes in the liver promote metabolic control, immunological modulation, fibrosis development, and the pathogenesis of hepatocellular carcinoma via modulating interactions among hepatocytes, Kupffer cells, and hepatic stellate cells. Furthermore, exosomes function as potential diagnostic biomarkers, with their molecular content indicative of disease conditions such as viral hepatitis, non-alcoholic fatty liver disease (NAFLD), and hepatocellular cancer. Recent advancements in exosome engineering, including targeted surface alterations, hybrid vesicle technologies, and hydrogel-based delivery methods, have shown their therapeutic promise for precision medicine. However, challenges such as heterogeneity in exosome isolation, cargo variability, off-target effects, and immunogenicity pose translational barriers. The standardization of isolation procedures, enhancement of cargo-loading tactics, and establishment of regulatory frameworks are essential for their clinical use. Overcoming these restrictions will enable exosome-based precision diagnostics and therapies, establishing them as leaders in next-generation regenerative medicine and tailored drug delivery. This study distinctly highlights the use of modified exosomes in liver disorders, integrating biogenesis mechanisms with novel treatment approaches and delivery systems.