The Application Potential and Future Challenges of Plant-Derived Exosome-like Nanoparticles in the Treatment of Liver Diseases

Liver disease is a serious global health challenge, with high morbidity and mortality that put significant socioeconomic stress on society. Despite therapeutic advances, current regimens have been limited by rapid drug resistance and insufficient targeting accuracy, and there is an urgent need for new methods. Plant-derived exosome-like nanoparticles (PELNs) are a promising natural nanotherapeutic platform due to their low immunogenicity, high biocompatibility, and prolonged stability in biological fluids. We review the biological sources, basic properties, and key preparative techniques for PELNs and characterize their mechanisms of action and therapeutic use in common liver diseases. We analyze their multiple-target hepatoprotective mechanisms including liver-specific targeting pathways and reducing critical inflammatory and antioxidant cascades. We summarize the therapeutic performance of different PELNs in major hepatic models including hepatocellular carcinoma, hepatic fibrosis, alcohol-related liver disease, and acute liver failure, highlighting key plant sources, primary biological effects, and precise molecular pathways. Moreover, one of the major methodological contributions of this work is the proposal of a new recommended extraction framework based on differential and density gradient centrifugation, optimized specifically for different plant tissue types (leaves, roots/stems, and fruits) to minimize technical heterogeneity. Finally, we discuss the major challenges that impede clinical translation of these nanovesicles, including incompletely elucidated mechanisms, imperfect manufacturing practices, and inadequate safety evaluation mechanisms, pointing to important, useful directions for future applications in hepatology.