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Research Article

Application of biocompatible custom ceria nanoparticles in improving the quality of liver grafts for transplantation

Yinbiao Qiao1,2,§, Jianhui Li2,3,4,§, Suchen Bian1,2, Chenyue Zhan1, Jia Luo1,2, Li Jiang1,2, Haoyu Li2, Hao Wu1, Cheng Zhang1, Shusen Zheng1,2( ), Haiyang Xie1,2( ), Penghong Song1,2( )
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
National Health Commission (NHC) Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou 310015, China
The Organ Repair and Regeneration Medicine Institute of Hangzhou, Hangzhou 310003, China

§ Yinbiao Qiao and Jianhui Li contributed equally to this work.

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Graphical Abstract

Organ protection techniques improve the quality and the prognosis of recipients in clinical, alleviating the shortage of organs for transplantation. Ceria nanoparticles, as excellent antioxidant, are promising organ-protective agent that can improve the quality of liver grafts by alleviating the ischemia-reperfusion injury.

Abstract

Liver transplantation (LT), an ultimate and vital method for treating end-stage liver disease, is often accompanied by ischemia-reperfusion injury (IRI) resulting from warm or cold ischemia of the donor liver. Organ protection techniques are used to improve the quality of liver grafts (from retrieval to implantation). Reactive oxygen species (ROS) cause oxidative stress, which is considered a crucial factor in IRI after LT. Nano antioxidants capable of scavenging ROS alleviate IRI in multiple types of organs and tissues. In this study, we synthesized ceria nanoparticles (NPs) with antioxidant properties using a pyrolysis method and covered them with phospholipid-polyethylene glycol to improve their biocompatibility in vivo. We investigated the potential organ-protective effect of ceria NPs and the underlying mechanisms. Ceria NPs promoted liver function recovery after LT by attenuating IRI in liver grafts in vivo. The protective effect of ceria NPs on liver grafts was investigated by applying hypothermic oxygenated machine perfusion ex vivo. Ceria NPs attenuated hypoxia reoxygenation- or H2O2-induced hepatocyte injury by enhancing mitochondrial activity and ROS scavenging in vitro. These effects may be associated with the activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)/heme oxygenase 1 (HO-1) signaling pathway. In conclusion, ceria NPs may serve as a promising antioxidant agent for the treatment of hepatic IRI after LT.

Keywords

ceria nanoparticlesliver transplantationhypothermic oxygenated machine perfusion (HOPE)ischemia-reperfusion injury (IRI)antioxidant

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Nano Research
Volume 16 Issue 4,
April 2023
Pages 5176-5188
DOI: 10.1007/s12274-022-5071-2
Cite this article:
Qiao Y, Li J, Bian S, et al. Application of biocompatible custom ceria nanoparticles in improving the quality of liver grafts for transplantation. Nano Research, 2023, 16(4): 5176-5188. https://doi.org/10.1007/s12274-022-5071-2
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Received: 02 August 2022
Revised: 19 September 2022
Accepted: 19 September 2022
Published: 23 November 2022
© Tsinghua University Press 2022
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