title: Parallel Comparative Studies on Mouse Toxicity of Oxide Nanoparticle- and Gadolinium-Based T1 MRI Contrast Agents.
abstract: Magnetic resonance imaging (MRI) contrast agents with high relaxivity are highly desirable because they can significantly increase the accuracy of diagnosis. However, they can be potentially toxic to the patients. In this study, using a mouse model, we investigate the toxic effects and subsequent tissue damage induced by three T1 MRI contrast agents: gadopentetate dimeglumine injection (GDI), a clinically used gadolinium (Gd)-based contrast agent (GBCAs), and oxide nanoparticle (NP)-based contrast agents, extremely small-sized iron oxide NPs (ESIONs) and manganese oxide (MnO) NPs. Biodistribution, hematological and histopathological changes, inflammation, and the endoplasmic reticulum (ER) stress responses are evaluated for 24 h after intravenous injection. These thorough assessments of the toxic and stress responses of these agents provide a panoramic description of safety concerns and underlying mechanisms of the toxicity of contrast agents in the body. We demonstrate that ESIONs exhibit fewer adverse effects than the MnO NPs and the clinically used GDI GBCAs, providing useful information on future applications of ESIONs as potentially safe MRI contrast agents.
authors.affiliation: CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China , Beijing 100190, P. R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou 310058, P. R. China.|Key Laboratory of Biomedical Engineering of the Ministry of Education, Zhejiang University , Hangzhou 310058, P. R. China.|Center for Nanoparticle Research, Institute for Basic Science (IBS) , Seoul 151-742, Korea.|School of Chemical and Biological Engineering, Seoul National University , Seoul 151-742, Korea.
authors.forename: Daishun
authors.initials: D
authors.lastname: Ling
authors.affiliation: CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China , Beijing 100190, P. R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou 310058, P. R. China.
authors.forename: Shuaifei
authors.initials: S
authors.lastname: Wang
authors.affiliation: CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China , Beijing 100190, P. R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China , Beijing 100190, P. R. China.
authors.forename: Ru
authors.initials: R
authors.lastname: Bai
authors.affiliation: Center for Nanoparticle Research, Institute for Basic Science (IBS) , Seoul 151-742, Korea.|School of Chemical and Biological Engineering, Seoul National University , Seoul 151-742, Korea.
authors.forename: Seungmin
authors.initials: S
authors.lastname: Baik
authors.affiliation: CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China , Beijing 100190, P. R. China.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China , Beijing 100190, P. R. China.
authors.forename: Chunying
authors.initials: C
authors.lastname: Chen
authors.affiliation: Center for Nanoparticle Research, Institute for Basic Science (IBS) , Seoul 151-742, Korea.|School of Chemical and Biological Engineering, Seoul National University , Seoul 151-742, Korea.
authors.forename: Taeghwan
authors.initials: T
authors.lastname: Hyeon
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003287:Contrast Media / Q000737:chemistry / Q000633:toxicity*; D005682:Gadolinium / Q000737:chemistry / Q000633:toxicity*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D058185:Magnetite Nanoparticles; D005682:Gadolinium
keywords: biodistribution; contrast agent; endoplasmic reticulum stress; iron oxide nanoparticles; magnetic resonance imaging; toxicity evaluation