title: Cerium Oxide Nanoparticles: A Potential Medical Countermeasure to Mitigate Radiation-Induced Lung Injury in CBA/J Mice.
abstract: Cerium oxide nanoparticles (CNPs) have a unique surface regenerative property and can efficiently control reactive oxygen/nitrogen species. To determine whether treatment with CNPs can mitigate the delayed effects of lung injury after acute radiation exposure, CBA/J mice were exposed to 15 Gy whole-thorax radiation. The animals were either treated with nanoparticles, CNP-18 and CNP-ME, delivered by intraperitoneal injection twice weekly for 4 weeks starting 2 h postirradiation or received radiation treatment alone. At the study's end point of 160 days, 90% of the irradiated mice treated with high-dose (10 μM) CNP-18 survived, compared to 10% of mice in the radiation-alone (P < 0.0001) and 30% in the low-dose (100 nM) CNP-18. Both low- and high-dose CNP-ME-treated irradiated mice showed increased survival rates of 40% compared to 10% in the radiation-alone group. Multiple lung functional parameters recorded by flow-ventilated whole-body plethysmography demonstrated that high-dose CNP-18 treatment had a significant radioprotective effect on lethal dose radiation-induced lung injury. Lung histology revealed a significant decrease (P < 0.0001) in structural damage and collagen deposition in mice treated with high-dose CNP-18 compared to the irradiated-alone mice. In addition, significant reductions in inflammatory response (P < 0.01) and vascular damage (P < 0.01) were observed in the high-dose CNP-18-treated group compared to irradiated-alone mice. Together, the findings from this preclinical efficacy study clearly demonstrate that CNPs have both clinically and histologically significant mitigating and protective effects on lethal dose radiation-induced lung injury.
authors.affiliation: a   Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland 21201;
authors.forename: P-T
authors.initials: PT
authors.lastname: Xu
authors.affiliation: b   Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia 22908; and.
authors.forename: B W
authors.initials: BW
authors.lastname: Maidment
authors.affiliation: a   Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland 21201;
authors.forename: V
authors.initials: V
authors.lastname: Antonic
authors.affiliation: a   Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland 21201;
authors.forename: I L
authors.initials: IL
authors.lastname: Jackson
authors.forename: S
authors.initials: S
authors.lastname: Das
authors.affiliation: a   Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland 21201;
authors.forename: A
authors.initials: A
authors.lastname: Zodda
authors.affiliation: a   Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland 21201;
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: c   Advanced Materials Processing and Analysis Center, Nanoscience Technology Center, Materials Science and Engineering, University of Central Florida, Orlando, Florida 32826.
authors.forename: S
authors.initials: S
authors.lastname: Seal
authors.affiliation: a   Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland 21201;
authors.forename: Z
authors.initials: Z
authors.lastname: Vujaskovic
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000528:radiation effects; D002563:Cerium / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D055370:Lung Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009929:Organ Size / Q000187:drug effects / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D012119:Respiration / Q000187:drug effects / Q000528:radiation effects; D016019:Survival Analysis
chemical_list: D002563:Cerium; C030583:ceric oxide