PEGylated bilirubin-coated iron oxide nanoparticles as a biosensor for magnetic relaxation switching-based ros detection in whole blood

Dong Yun Lee, Sukmo Kang, Yonghyun Lee, Jin Yong Kim, Dohyun Yoo, Wonsik Jung, Soyoung Lee, Yong Yeon Jeong, Kwangyeol Lee, Sangyong Jon

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)


Rationale: Magnetic relaxation switching (MRSw) induced by target-triggered aggregation or dissociation of superparamagnetic iron oxide nanoparticles (SPIONs) have been utilized for detection of diverse biomarkers. However, an MRSw-based biosensor for reactive oxygen species (ROS) has never been documented. Methods: To this end, we constructed a biosensor for ROS detection based on PEGylated bilirubin (PEG-BR)-coated SPIONs (PEG-BR@SPIONs) that were prepared by simple sonication via ligand exchange. In addition, near infra-red (NIR) fluorescent dye was loaded onto PEG-BR@SPIONs as a secondary option for fluorescence-based ROS detection. Results: PEG-BR@SPIONs showed high colloidal stability under physiological conditions, but upon exposure to the model ROS, NaOCl, in vitro, they aggregated, causing a decrease in signal intensity in T2-weighted MR images. Furthermore, ROS-responsive PEG-BR@SPIONs were taken up by lipopolysaccharide (LPS)-activated macrophages to a much greater extent than ROS-unresponsive control nanoparticles (PEG-DSPE@SPIONs). In a sepsis-mimetic clinical setting, PEG-BR@SPIONs were able to directly detect the concentrations of ROS in whole blood samples through a clear change in T2 MR signals and a 'turn-on' signal of fluorescence. Conclusions: These findings suggest that PEG-BR@SPIONs have the potential as a new type of dual mode (MRSw-based and fluorescence-based) biosensors for ROS detection and could be used to diagnose many diseases associated with ROS overproduction.

Original languageEnglish
Pages (from-to)1997-2007
Number of pages11
Issue number5
Publication statusPublished - 2020

Bibliographical note

Publisher Copyright:
© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.


  • Bilirubin nanoparticles
  • Biosensors
  • Iron oxide nanoparticles
  • Magnetic relaxation switching
  • Reactive oxygen species

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)


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