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.