title: Coulomb nanoradiator-mediated, site-specific thrombolytic proton treatment with a traversing pristine Bragg peak.
abstract: 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.
authors.affiliation: Departments of Biomedical Engineering, Catholic University of Daegu, School of Medicine, Daegu, Korea.
authors.forename: Jae-Kun
authors.initials: JK
authors.lastname: Jeon
authors.affiliation: Anatomy, and Diagnostic Imaging, Catholic University of Daegu, School of Medicine, Daegu, Korea.
authors.forename: Sung-Mi
authors.initials: SM
authors.lastname: Han
authors.affiliation: Catholic University of Daegu, School of Medicine, Daegu, Korea.
authors.forename: Soon-Ki
authors.initials: SK
authors.lastname: Min
authors.affiliation: Departments of Biomedical Engineering, Catholic University of Daegu, School of Medicine, Daegu, Korea.
authors.forename: Seung-Jun
authors.initials: SJ
authors.lastname: Seo
authors.affiliation: Pohang Accelerator Laboratory, Pohang, Korea.
authors.forename: Kyuwook
authors.initials: K
authors.lastname: Ihm
authors.affiliation: Departments of Biomedical Engineering, Catholic University of Daegu, School of Medicine, Daegu, Korea.
authors.forename: Won-Seok
authors.initials: WS
authors.lastname: Chang
authors.affiliation: Departments of Biomedical Engineering, Catholic University of Daegu, School of Medicine, Daegu, Korea.
authors.forename: Jong-Ki
authors.initials: JK
authors.lastname: Kim
mesh_terms: D000818:Animals; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D005290:Ferric Compounds / Q000008:administration & dosage* / Q000737:chemistry; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D051379:Mice; D036103:Nanotechnology; D061766:Proton Therapy / Q000295:instrumentation*; D011829:Radiation Dosage; D017382:Reactive Oxygen Species / Q000378:metabolism; D013927:Thrombosis / Q000628:therapy*
chemical_list: D005290:Ferric Compounds; D017382:Reactive Oxygen Species; C000499:ferric oxide