Detection and Mapping of Lipids From Selected Food‐Derived Exosome‐Like Nanoparticles Through LC–MS Analysis

ABSTRACT Dietary plant‐derived exosome‐like nanoparticles (ELNs) are nanosized lipid membrane vesicles with the ability to elicit diverse biological responses in recipient cells. There has been impressive progress in the characterization and compositional analysis of ELNs from numerous sources, with a main focus on nucleic acids and proteins. Lipids are also important components of ELNs and are relevant to regulatory and pharmacological aspects; however, comparative assessments of ELN lipidomes are lacking. Here, we have sought to understand variations in the lipidomic landscape of ELNs from grapes, ginger, and garlic using LC–MS analysis. Glycerophospholipids and fatty acyls constituted the dominant lipid classes in these ELNs. Upon analysis of species‐specific abundances of important classes, ginger‐derived ELNs were distinguished by a higher abundance of sphingolipids with the unique presence of subclasses such as sphingomyelins, gangliosides, and acidic glycosphingolipids. Grape ELNs were characterized by elevated phosphatidic acid (PA) and phosphatidylglycerol (PG) levels. Garlic ELNs had slightly higher levels of phosphatidylethanolamine (PE). Ginger and grape ELNs also showed increased levels of diacylglycerols (DAG) and triacylglycerols (TAG) compared to garlic ELNs. Sterol and prenol lipids were more abundant in garlic and grape ELNs than in ginger ELNs. Multivariate analyses revealed distinct lipidomic signatures that reliably distinguished ELNs by plant origin.This study provides a systematic comparison of lipidomes across dietary ELNs, identifying source‐specific lipid features that may underlie their differential stability, uptake, and biological activity, and highlighting the relevance of ELN lipids in biomedical and nutraceutical applications.