Bioinspired grape-derived exosome-liposome hybrid nanoparticles for attenuating acetaminophen-induced liver injury

Acetaminophen (APAP) overdose remains a leading cause of drug-induced acute liver injury and acute liver failure. Plant-derived exosome-like nanovesicles have attracted increasing interest as bioactive and biocompatible nanomaterials, while liposomes offer tunable physicochemical properties and formulation control. Here, we report a bioinspired hybrid nanoplatform, the Fusion Nanoparticles (Fusion NPs), generated by fusing grape-derived exosome-like particles (GELPs) with liposomes. This design was intended to improve the protective performance of liposomes alone by incorporating grape-derived exosome-like particles with antioxidant and anti-inflammatory potential. Fusion NPs exhibited nanoscale vesicular morphology, altered physicochemical properties compared with liposomes alone, and detectable cell-associated dual fluorescence in HepG2 cells. In a HepG2 high-APAP stress screening model, Fusion NP treatment improved population-level cell viability and reduced total reactive oxygen species and superoxide-associated fluorescence signals compared with APAP-treated controls. In vivo, Fusion NPs were evaluated in a mouse APAP challenge model using a delayed day-21 endpoint. The animal data provides exploratory late-endpoint observations under the experimental conditions used. Overall, this study presents a GELP–liposome hybrid nanoparticle platform with preliminary antioxidant stress-modulating and tissue-associated protective potential, while highlighting the need for future validation in metabolically competent hepatocyte models and early in vivo APAP injury time points.