Departments of Biomedical Engineering, Catholic University of Daegu, School of Medicine, Daegu, Korea.
Anatomy, and Diagnostic Imaging, Catholic University of Daegu, School of Medicine, Daegu, Korea.
Sci Rep. 2016 Nov 29;6:37848. doi: 10.1038/srep37848.
Traversing proton beam-irradiated, mid/high-Z nanoparticles produce site-specific enhancement of X-ray photon-electron emission via the Coulomb nanoradiator (CNR) effect, resulting in a nano- to micro-scale therapeutic effect at the nanoparticle-uptake target site. Here, we demonstrate the uptake of iron oxide nanoparticles (IONs) and nanoradiator-mediated, site-specific thrombolysis without damaging the vascular endothelium in an arterial thrombosis mouse model. The enhancement of low-energy electron (LEE) emission and reactive oxygen species (ROS) production from traversing proton beam-irradiated IONs was examined. Flow recovery was only observed in CNR-treated mice, and greater than 50% removal of the thrombus was achieved. A 2.5-fold greater reduction in the thrombus-enabled flow recovery was observed in the CNR group compared with that observed in the untreated ION-only and proton-only control groups (p < 0.01). Enhancement of the X-ray photon-electron emission was evident from both the pronounced Shirley background in the electron yield and the 1.2- to 2.5-fold enhanced production of ROS by the proton-irradiated IONs, which suggests chemical degradation of the thrombus without potent emboli.
穿越质子束辐照的中/高 Z 纳米颗粒通过库仑纳米辐射器（CNR）效应产生特定于位点的 X 射线光子-电子发射增强，从而在纳米颗粒摄取靶位点处产生纳米到微米级的治疗效果。在这里，我们在动脉血栓形成的小鼠模型中证明了氧化铁纳米颗粒（IONs）的摄取和纳米辐射器介导的、特定于位点的溶栓作用，而不会损伤血管内皮。研究了穿越质子束辐照的 IONs 产生的低能电子（LEE）发射和活性氧物种（ROS）产生的增强。仅在 CNR 处理的小鼠中观察到血流恢复，并且实现了超过 50%的血栓去除。与未处理的 ION 仅和质子仅对照组相比，在 CNR 组中观察到血栓恢复的降低幅度增加了 2.5 倍（p < 0.01）。从电子产额中明显的 Shirley 背景以及质子辐照的 IONs 产生的 ROS 增强 1.2 到 2.5 倍，明显增强了 X 射线光子-电子发射，这表明血栓的化学降解而没有强烈的栓塞。
