Mesoporous Hollow Manganese Doped Ceria Nanoparticle for Effectively Prevention of Hepatic Ischemia Reperfusion Injury

Peiru Si,1 Jiaxing Lei,1 Chen Yang,1 Peipei Zhang,1 Xiaojiao Li,2 Shaohua Zheng,3 Qingqing Li,1 Jiye Zhang1 1School of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Biobank, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 3Department of Anesthesiology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Qingqing Li; Jiye Zhang, School of Pharmacy, Health Science Center, Xi’an Jiaotong University, No. 76 Yanta Westroad, Xi’an, People’s Republic of China, Email liqingqing0217@xjtu.edu.cn; zjy2011@xjtu.edu.cnIntroduction: Hepatic ischemia-reperfusion injury (HIRI) is the main reason for liver dysfunction or failure after liver resection and liver transplantation. As excess accumulation of reactive oxygen species (ROS) is the leading factor, ceria nanoparticle, a cyclic reversible antioxidant, is an excellent candidate for HIRI.Methods: Manganese doped mesoporous hollow ceria nanoparticles (MnOx-CeO2 NPs) were prepared, and the physicochemical characteristics, such as particle size, morphology, microstructure, etc. were elucidated. The in vivo safety and liver targeting effect were examined after i.v. injection. The anti-HIRI was determined by a mouse HIRI model.Results: MnOx-CeO2 NPs with 0.40% Mn doped exhibited the strongest ROS-scavenging capability, which may due to the increased specific surface area and surface oxygen concentration. The nanoparticles accumulated in the liver after i.v. injection and exhibited good biocompatibility. In the HIRI mice model, MnOx-CeO2 NPs significantly reduced the serum ALT and AST level, decreased the MDA level and increased the SOD level in the liver, prevent pathological damages in the liver.Conclusion: MnOx-CeO2 NPs were successfully prepared and it could significantly inhibit the HIRI after i.v. injection.Graphical Abstract: Keywords: hepatic ischemia reperfusion injury, Mn-doped mesoporous hollow cerium oxide nanoparticles, oxidative stress