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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.

Dong Yun Lee1,2, Sukmo Kang3,4,5, Yonghyun Lee3,4,5, Jin Yong Kim1,4,5, Dohyun Yoo3,4,5, Wonsik Jung3,4,5, Soyoung Lee3,4,5, Yong Yeon Jeong6, Kwangyeol Lee7, Sangyong Jon1,3,4,5, 

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