PEGylated bilirubin nanoparticle as an anti-oxidative and anti-inflammatory demulcent in pancreatic islet xenotransplantation

Min Jun Kim, Yonghyun Lee, Sangyong Jon, Dong Yun Lee

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


Transplanted islets suffer hypoxic stress, which leads to nonspecific inflammation. This is the major cause of islet graft failure during the early stage of intrahepatic islet transplantation. Although bilirubin has shown potent anti-oxidative and anti-inflammatory functions, its clinical applications have been limited due to its insolubility and short half-life. To overcome this problem, novel amphiphilic bilirubin nanoparticles are designed. Hydrophilic poly(ethylene glycol) (PEG) is conjugated to the hydrophobic bilirubin molecule. Then, the PEG-bilirubin conjugates form nanoparticles via self-assembly, i.e., so-called to BRNPs. BRNPs can protect islet cells not only from chemically induced oxidative stress by scavenging reactive oxygen species molecules, but also from activated macrophages by suppressing cytokine release. Importantly, in vivo experiments demonstrate that BRNP treatment can dramatically and significantly prolong islet graft survival compared to bilirubin treatment. In addition, immunohistochemical analysis shows BRNPs have potent anti-oxidative and anti-inflammatory capabilities. Collectively, novel BRNPs can be a new potent remedy for successful islet transplantation.

Original languageEnglish
Pages (from-to)242-252
Number of pages11
StatePublished - 1 Jul 2017

Bibliographical note

Funding Information:
This study was supported by a grant from the National Leading Research Laboratory (NRF-2015R1A2A1A05001832) and from Basic Science Research Program (NRF-2015M3A9E2030125) through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning, Korea Government. The authors declare no competing financial interest.

Publisher Copyright:
© 2017 Elsevier Ltd


  • Hypoxia
  • Inflammation
  • Pancreatic islet
  • PEGylated bilirubin nanoparticles (BRNPs)
  • Reactive oxygen species (ROS)


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