Lipidomic analysis of plant-derived extracellular vesicles for guidance of potential anti-cancer therapy

Plant-derived extracellular vesicles (PEVs) have been regarded as a superior source for nanomedicine and drug delivery systems. Nevertheless, their clinical translation is hindered by the lack of clarity and even contradiction in their biomedical applications. Herein, we conducted a comprehensive compositional analysis of four commonly used PEVs to fully understand their functional lipid contents and assess their potential therapeutic applications. The lipidomic analysis revealed the presence of cytotoxic gingerols and shogaols in ginger-derived EVs (GEVs). Subsequent <i>in vitro</i> and <i>in vivo</i> investigations substantiated the remarkable tumor cell inhibitory and tumor growth suppression efficacy of GEVs. The transcriptomic analysis indicated that GEVs regulate the cell cycle and p53 signaling pathways, thereby inducing cancer cell apoptosis. The supplementary proteomic analysis suggested the potential protein markers in PEV research. These findings highlight the value of multi-omics analyses in elucidating the potential therapeutic effects of PEVs and in advancing the development of PEV-based therapies.