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Theranostics 2020; 10(5):1997-2007. doi:10.7150/thno.39662 This issue Cite

Research Paper

PEGylated Bilirubin-coated Iron Oxide Nanoparticles as a Biosensor for Magnetic Relaxation Switching-based ROS Detection in Whole Blood

Dong Yun Lee^1,2, Sukmo Kang^3,4,5, Yonghyun Lee^3,4,5, Jin Yong Kim^1,4,5, Dohyun Yoo^3,4,5, Wonsik Jung^3,4,5, Soyoung Lee^3,4,5, Yong Yeon Jeong⁶, Kwangyeol Lee⁷, Sangyong Jon^1,3,4,5,✉

1. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon 34141, Republic of Korea
2. Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, OLYMPIC-RO 43-GIL, Seoul 05505, Republic of Korea
3. Department of Biological Sciences, KAIST, 291 Daehak-ro, Daejeon 34141, Republic of Korea
4. KAIST Institute for BioCentury, KAIST, 291 Daehak-ro, Daejeon 34141, Republic of Korea
5. Center for Precision Bio-Nanomedicine, KAIST, 291 Daehak-ro, Daejeon 34141, Republic of Korea
6. Department of Radiology, Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun 58128, Republic of Korea
7. Department of Chemistry, Korea University, 145 Anam-ro, Seoul 02841, Republic of Korea

✉ Corresponding author: Sangyong Jon. Phone: +82-10-47210602; Fax: +82-42-3504450; E-mail: syjonac.kr

Abstract

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.

Keywords: Bilirubin nanoparticles, Biosensors, Iron oxide nanoparticles, Magnetic relaxation switching, Reactive oxygen species

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