TY - JOUR
T1 - Parallel Comparative Studies on Mouse Toxicity of Oxide Nanoparticle- and Gadolinium-Based T1 MRI Contrast Agents
AU - Chen, Rui
AU - Ling, Daishun
AU - Zhao, Lin
AU - Wang, Shuaifei
AU - Liu, Ying
AU - Bai, Ru
AU - Baik, Seungmin
AU - Zhao, Yuliang
AU - Chen, Chunying
AU - Hyeon, Taeghwan
N1 - Funding Information:
T.H. acknowledges financial support by the Research Center Program of the Institute for Basic Science (IBS) in Korea (IBS-R006-D1); D.L. acknowledges the National Natural Science Foundation of China (51503180), “Thousand Talents Program” for Distinguished Young Scholars (588020*G81501/048) and Fundamental Research Funds for the Central Universities (520002*172210151); R.C., C.C., and Y.Z. acknowledge financial support by the Ministry of Science and Technology of China (2011CB933401 and 2012CB934003), the National Natural Science Foundation of China (21477029, 21320102003, 21277037, 21277080), the Chinese Academy of Sciences (XDA09040400), Major Project of the National Social Science Fund (Grant No. 12&ZD117) “Ethical issues of hightech,” Beijing Key Laboratory of Environmental Toxicology(2015HJDL01) and the National Science Fund for Distinguished Young Scholars (11425520).
Publisher Copyright:
© 2015 American Chemical Society.
PY - 2015/11/15
Y1 - 2015/11/15
N2 - 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.
AB - 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.
KW - biodistribution
KW - contrast agent
KW - endoplasmic reticulum stress
KW - iron oxide nanoparticles
KW - magnetic resonance imaging
KW - toxicity evaluation
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U2 - 10.1021/acsnano.5b05783
DO - 10.1021/acsnano.5b05783
M3 - Article
C2 - 26567968
AN - SCOPUS:84952332753
SN - 1936-0851
VL - 9
SP - 12425
EP - 12435
JO - ACS Nano
JF - ACS Nano
IS - 12
ER -