Biomimetic hybrid nanoparticles from grape-derived exosome-like particles and liposomes potentiate JQ1-mediated anti-fibrotic effects in hepatic stellate cells.

Activated hepatic stellate cells (HSCs) play a central role in liver fibrosis by promoting extracellular matrix deposition, oxidative stress, and pro-fibrotic signaling. Here, we engineered a membrane-fused hybrid nanoparticle by combining grape-derived exosome-like particles (GELPs) with liposomes to encapsulate JQ1, termed Hybrid@JQ1, and evaluated its anti-fibrotic effects in TGF-β1-activated LX-2 cells. GELPs were successfully isolated and characterized, while the formation of GELP-liposome hybrid nanoparticles were verified by nanoparticle characterization and colocalization analysis. Hybrid@JQ1 exhibited good physicochemical stability and enhanced cellular uptake. In vitro, Hybrid@JQ1 inhibited LX-2 cell proliferation and migration, decreased collagen accumulation, and suppressed α-SMA expression. qPCR gene expression profile further showed that Hybrid@JQ1 downregulated multiple fibrosis-related genes, including α-SMA, COL1A1, COL3A1, and TGF-β, as well as inflammation- and oxidative stress-associated genes such as NOX4, IL6, and TNF-α. These findings indicate that GELP-liposome hybridization is an effective strategy for JQ1 delivery and that Hybrid@JQ1 alleviates fibrotic phenotypes in activated HSCs in vitro. Our study provides a promising plant-derived biomimetic nanoplatform for anti-fibrotic drug delivery.