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

51 Scopus citations

Abstract

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
JournalBiomaterials
Volume133
DOIs
StatePublished - 1 Jul 2017

Keywords

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

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