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Open AccessArticle

Targeted Delivery of Iron Oxide Nanoparticle-Loaded Human Embryonic Stem Cell-Derived Spherical Neural Masses for Treating Intracerebral Hemorrhage

1
Department of Neurology, Seoul National University Hospital, Seoul 03080, Korea
2
Department of Neurology, Seoul National University College of Medicine, Seoul 03080, Korea
3
Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea
4
Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Korea
5
School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 08826, Korea
6
School of Advanced Materials Engineering, Kookmin University, Seoul 02707, Korea
7
Research and Development Center, Jeil Pharmaceutical Co. Ltd., Yongin-si, Gyeonggi-do 17172, Korea
8
Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University, Seoul 08826, Korea
9
Department of Neurology, Hallym University Dongtan Sacred Heart Hospital, Gyeonggi-do 14068, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(10), 3658; https://doi.org/10.3390/ijms21103658
Received: 6 May 2020 / Revised: 13 May 2020 / Accepted: 20 May 2020 / Published: 22 May 2020
(This article belongs to the Special Issue Neuroprotective Strategies 2020)
This study evaluated the potential of iron oxide nanoparticle-loaded human embryonic stem cell (ESC)-derived spherical neural masses (SNMs) to improve the transportation of stem cells to the brain, ameliorate brain damage from intracerebral hemorrhage (ICH), and recover the functional status after ICH under an external magnetic field of a magnet attached to a helmet. At 24 h after induction of ICH, rats were randomly separated into three experimental groups: ICH with injection of phosphate-buffered saline (PBS group), ICH with intravenous injection of magnetosome-like ferrimagnetic iron oxide nanocubes (FION)-labeled SNMs (SNMs* group), and ICH with intravenous injection of FION-labeled SNMs followed by three days of external magnetic field exposure for targeted delivery by a magnet-embedded helmet (SNMs*+Helmet group). On day 3 after ICH induction, an increased Prussian blue-stained area and decreased swelling volume were observed in the SNMs*+Helmet group compared with that of the other groups. A significantly decreased recruitment of macrophages and neutrophils and a downregulation of pro-inflammatory cytokines followed by improved neurological function three days after ICH were observed in the SNMs*+Helmet group. Hemispheric atrophy at six weeks after ICH was significantly decreased in the SNMs*+Helmet group compared with that of the PBS group. In conclusion, we have developed a targeted delivery system using FION tagged to stem cells and a magnet-embedded helmet. The targeted delivery of SNMs might have the potential for developing novel therapeutic strategies for ICH. View Full-Text
Keywords: iron oxide nanoparticle; human embryonic stem cell; spherical neural masses; magnet-embedded helmet; targeted delivery; intracerebral hemorrhage iron oxide nanoparticle; human embryonic stem cell; spherical neural masses; magnet-embedded helmet; targeted delivery; intracerebral hemorrhage
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Kang, M.K.; Kim, T.J.; Kim, Y.-J.; Kang, L.; Kim, J.; Lee, N.; Hyeon, T.; Lim, M.-S.; Mo, H.J.; Shin, J.H.; Ko, S.-B.; Yoon, B.-W. Targeted Delivery of Iron Oxide Nanoparticle-Loaded Human Embryonic Stem Cell-Derived Spherical Neural Masses for Treating Intracerebral Hemorrhage. Int. J. Mol. Sci. 2020, 21, 3658.

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