Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon 34141, Republic of Korea.
Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, OLYMPIC-RO 43-GIL, Seoul 05505, Republic of Korea.
Theranostics. 2020 Jan 12;10(5):1997-2007. doi: 10.7150/thno.39662. eCollection 2020.
: 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. : 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. Resul: PEG-BR@SPIONs showed high colloidal stability under physiological conditions, but upon exposure to the model ROS, NaOCl, , 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. : 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.
基于超顺磁性氧化铁纳米粒子（SPIONs）的目标触发聚集或解离引起的磁弛豫切换（MRSw）已被用于检测多种生物标志物。然而，基于 MRSw 的活性氧（ROS）生物传感器从未有过记录。
为此，我们构建了一种基于聚乙二醇化胆红素（PEG-BR）涂层 SPIONs（PEG-BR@SPIONs）的 ROS 检测生物传感器，该传感器是通过简单的超声通过配体交换制备的。此外，近红外（NIR）荧光染料被加载到 PEG-BR@SPIONs 上，作为基于荧光的 ROS 检测的二级选项。
PEG-BR@SPIONs 在生理条件下表现出高胶体稳定性，但暴露于模型 ROS NaOCl 时，它们会聚集，导致 T2 加权 MR 图像中的信号强度降低。此外，ROS 响应性 PEG-BR@SPIONs 被脂多糖（LPS）激活的巨噬细胞摄取的程度远远大于非 ROS 响应性对照纳米颗粒（PEG-DSPE@SPIONs）。在模拟脓毒症的临床环境中，PEG-BR@SPIONs 能够通过 T2 MR 信号的明显变化和荧光的“开启”信号，直接检测全血样本中的 ROS 浓度。
这些发现表明，PEG-BR@SPIONs 具有作为新型双模式（基于 MRSw 和基于荧光）ROS 检测生物传感器的潜力，并可用于诊断与 ROS 过度产生相关的许多疾病。
