Curcumin-Loaded Mesenchymal Stem Cell-Derived Exosomes: A Potential Effective Strategy for NAFLD

The aim of this study was to construct curcumin-loaded mesenchymal stem cell-derived exosomes (Cur-exos) and explore their effects on nonalcoholic fatty liver disease (NAFLD) models both in vitro and in vivo. Cur-exos were prepared using three common drug-loading techniques—incubation, sonication, and freeze–thaw cycles. Among these, Cur-exos prepared via repeated freeze–thawing demonstrated higher encapsulation efficiency and drug-loading rates than those produced by other methods. In vitro, Cur-exos exhibited enhanced stability, were efficiently taken up by hepatocytes, and mitigated palmitic acid (PA)–induced lipotoxicity in HepG2 cells. Moreover, Cur-exos significantly ameliorated liver damage in NAFLD model mice, reduced inflammation, decreased reactive oxygen species (ROS) levels, and mitigated endoplasmic reticulum (ER) stress. Additionally, Cur-exos effectively regulated lipid metabolism disorders and improved impaired glucose tolerance. Overall, we demonstrate that, compared with free curcumin, Cur-exos significantly improve curcumin stability and offer superior therapeutic effects in NAFLD mouse models. This study provides a novel approach for developing treatments for NAFLD.