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Nano Research

Article Title

Biocompatible custom ceria nanoparticles against reactive oxygen species resolve acute inflammatory reaction after intracerebral hemorrhage

Authors

Dong-Wan Kang, Laboratory of Innovative Nanobiotechnology, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea Department of Neurology, Seoul National University Hospital, Seoul 03080, Republic of Korea
Chi Kyung Kim, Laboratory of Innovative Nanobiotechnology, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea Department of Neurology, Korea University Guro Hospital and Korea University College of Medicine, Seoul 08308, Republic of Korea
Han-Gil Jeong, Laboratory of Innovative Nanobiotechnology, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea Department of Neurology, Seoul National University Hospital, Seoul 03080, Republic of Korea
Min Soh, Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 151-742, Republic of Korea School of Chemical and Biological Engineering and Institute of Chemical Processes, Seoul National University, Seoul 151-742, Republic of Korea
Taeho Kim, Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 151-742, Republic of Korea School of Chemical and Biological Engineering and Institute of Chemical Processes, Seoul National University, Seoul 151-742, Republic of Korea
In-Young Choi, Laboratory of Innovative Nanobiotechnology, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea Department of Neurology, Seoul National University Hospital, Seoul 03080, Republic of Korea
Seul-Ki Ki, Laboratory of Innovative Nanobiotechnology, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea Department of Neurology, Seoul National University Hospital, Seoul 03080, Republic of Korea
Do Yeon Kim, Laboratory of Innovative Nanobiotechnology, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea Department of Neurology, Seoul National University Hospital, Seoul 03080, Republic of Korea
Wookjin Yang, Laboratory of Innovative Nanobiotechnology, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea Department of Neurology, Seoul National University Hospital, Seoul 03080, Republic of Korea
Taeghwan Hyeon, Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 151-742, Republic of Korea School of Chemical and Biological Engineering and Institute of Chemical Processes, Seoul National University, Seoul 151-742, Republic of Korea
Seung-Hoon Lee, Laboratory of Innovative Nanobiotechnology, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea Department of Neurology, Seoul National University Hospital, Seoul 03080, Republic of Korea

Keywords

ceria nanoparticles, intracerebral hemorrhage, free radical injury, anti-inflammation, neuroprotective agents, biomedical application

Abstract

ABSTRACT Intracerebral hemorrhage (ICH) is a devastating subtype of stroke with a high mortality rate, for which there currently is no effective treatment. A perihematomal edema caused by an intense inflammatory reaction is more deleterious than the hematoma itself and can result in neurological deterioration and death. Ceria nanoparticles (CeNPs) are potent free radical scavengers with potential for biomedical applications. As oxidative stress plays a major role in post-ICH inflammation, we hypothesized that CeNPs might protect against ICH. To test this hypothesis, core CeNPs were synthesized using a modified reverse micelle method and covered with phospholipid-polyethylene glycol (PEG) to achieve biocompatibility. We investigated whether our custom-made biocompatible CeNPs have protective effects against ICH. The CeNPs reduced oxidative stress, hemin-induced cytotoxicity, and inflammation in vitro. In a rodent ICH model, intravenously administered CeNPs were mainly distributed in the hemorrhagic hemisphere, suggesting that they could diffuse through the damaged blood–brain barrier. Moreover, CeNPs attenuated microglia/macrophage recruitment around the hemorrhagic lesion and inflammatory protein expression. Finally, CeNP treatment reduced the brain edema by 68.4% as compared to the control. These results reveal the great potential of CeNPs as a novel therapeutic agent for patients with ICH.

Graphical Abstract

Publisher

Tsinghua University Press

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