Introduction: Liver transplantation, a definitive solution for irreversible liver failure and malignant tumors, has encountered significant challenges predominantly attributable to sterile inflammation following ischemia-reperfusion injury caused by frail donor livers and inadequate preservation techniques. Ceria nanoparticles (CeO₂NPs) have antioxidant and anti-inflammatory effects, but their potential use in preserving donor livers remains unknown.
Methods: We created newly designed dextran-coated CeO₂NPs that we introduced to solutions used to infuse and preserve murine livers. The biodistribution of CeO₂NPs and their association with macrophages were investigated. Additionally, we used a liver transplantation mice model to investigate the roles of CeO₂NPs-containing preservation solution on liver injury, reactive oxygen species (ROS), inflammation infiltration, and hepatocyte apoptosis. In addition, both in vivo and in vitro studies were carried out to investigate the involvement of CeO₂NPs in the potential mechanisms of liver transplantation.
Results: The distribution of CeO₂NPs in different organs indicates their specificity in murine liver and Kupffer cells. Additionally, CeO₂NPs have been shown to improve liver injury, reduce ROS production and inflammation infiltration, and suppress hepatocyte apoptosis in mice that have undergone liver transplantation. Furthermore, the application of CeO₂NPs aligns with M2 macrophage polarization, implying that they alleviate sterile inflammation following donor liver implantation through interaction with M2 polarization.
Conclusion: A novel system for infusing and preserving donor livers can be accomplished by deploying CeO₂NPs in solution by alleviating sterile inflammation via M2 polarization, which may improve the prognosis of patients after liver transplantation in the near future.