Orally Deliverable Sequence-Targeted Fucoxanthin-Loaded Biomimetic Extracellular Vesicles for Alleviation of Nonalcoholic Fatty Liver Disease

Abstract

Extracellular vesicles (EVs) possess favorable biocompatibility and immunological characteristics, making them optimal carriers for bioactive substances. In this study, an innovative hepatic-targeted vesicle system encapsulating with fucoxanthin (GA-LpEVs-FX) was successfully designed and used to alleviate nonalcoholic fatty liver disease. The formulation entails the self-assembly of EVs derived from Lactobacillus paracasei (LpEVs), modification with glycyrrhetinic acid (GA) via amide reaction offering the system liver-targeting capacity and loading fucoxanthin (FX) through sonication treatment. In vitro experiments demonstrated that GA-LpEVs-FX effectively mitigated hepatic lipid accumulation and attenuated reactive oxygen species-induced damage resulting lipid accumulation (p < 0.05). In vivo, GA-LpEVs-FX exhibited significant downregulation of lipogenesis-related proteins, namely, fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC1), and sterol regulatory element binding protein 1 (SREBP-1), subsequently ameliorating lipid metabolism disorders (p < 0.05), and the stability of GA-LpEVs-FX significantly improved compared to free FX. These findings establish a novel formulation for utilizing foodborne components for nonalcoholic fatty liver disease alleviation.

Fucoxanthin Induces Ferroptosis in Cancer Cells via Downregulation of the Nrf2/HO−1/GPX4 Pathway

“…Fucoxanthin is an oxygenic carotenoid that widely exists in algae, marine phytoplankton, aquatic shellfish, and invertebrates [ 4 ]. Its molecular formula is C 42 H 58 O 6 , molecular mass is 658.91, and chemical structure is shown in Figure 1 A.…”