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

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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.

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References

  1. Qureshi, A. I.; Tuhrim, S.; Broderick, J. P.; Batjer, H. H.; Hondo, H.; Hanley, D. F. Spontaneous intracerebral hemorrhage. N. Engl. J. Med. 2001, 344, 1450–1460.

    Article  Google Scholar 

  2. Labovitz, D. L.; Halim, A.; Boden-Albala, B.; Hauser, W. A.; Sacco, R. L. The incidence of deep and lobar intracerebral hemorrhage in whites, blacks, and Hispanics. Neurology 2005, 65, 518–522.

    Article  Google Scholar 

  3. Qureshi, A. I.; Mendelow, A. D.; Hanley, D. F. Intracerebral haemorrhage. Lancet 2009, 373, 1632–1644.

    Article  Google Scholar 

  4. Hemphill, J. C.; Greenberg, S. M.; Anderson, C. S.; Becker, K.; Bendok, B. R.; Cushman, M.; Fung, G. L.; Goldstein, J. N.; Macdonald, R. L.; Mitchell, P. H. et al. Guidelines for the management of spontaneous intracerebral hemorrhage: A guideline for healthcare professionals from the American heart association/American stroke association. Stroke 2015, 46, 2032–2060.

    Article  Google Scholar 

  5. Mendelow, A. D.; Gregson, B. A.; Fernandes, H. M.; Murray, G. D.; Teasdale, G. M.; Hope, D. T.; Karimi, A.; Shaw, M. D. M.; Barer, D. H. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): A randomised trial. Lancet 2005, 365, 387–397.

    Article  Google Scholar 

  6. Mayer, S. A.; Brun, N. C.; Begtrup, K.; Broderick, J.; Davis, S.; Diringer, M. N.; Skolnick, B. E.; Steiner, T. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N. Engl. J. Med. 2008, 358, 2127–2137.

    Article  Google Scholar 

  7. Aronowski, J.; Zhao, X. R. Molecular pathophysiology of cerebral hemorrhage: Secondary brain injury. Stroke 2011, 42, 1781–1786.

    Article  Google Scholar 

  8. Masada, T.; Hua, Y.; Xi, G. H.; Yang, G. Y.; Hoff, J. T.; Keep, R. F. Attenuation of intracerebral hemorrhage and thrombin-induced brain edema by overexpression of interleukin-1 receptor antagonist. J. Neurosurg. 2001, 95, 680–686.

    Article  Google Scholar 

  9. Hua, Y.; Keep, R. F.; Hoff, J. T.; Xi, G. H. Brain injury after intracerebral hemorrhage: The role of thrombin and iron. Stroke 2007, 38, 759–762.

    Article  Google Scholar 

  10. Keep, R. F.; Hua, Y.; Xi, G. H. Intracerebral haemorrhage: Mechanisms of injury and therapeutic targets. Lancet Neurol. 2012, 11, 720–731.

    Article  Google Scholar 

  11. Dahle, J. T.; Arai, Y. Environmental geochemistry of cerium: Applications and toxicology of cerium oxide nanoparticles. Int. J. Environ. Res. Public Health 2015, 12, 1253–1278.

    Article  Google Scholar 

  12. Chen, J. P.; Patil, S.; Seal, S.; McGinnis, J. F. Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides. Nat. Nanotechnol. 2006, 1, 142–150.

    Article  Google Scholar 

  13. Das, M.; Patil, S.; Bhargava, N.; Kang, J.-F.; Riedel, L. M.; Seal, S.; Hickman, J. J. Auto-catalytic ceria nanoparticles offer neuroprotection to adult rat spinal cord neurons. Biomaterials 2007, 28, 1918–1925.

    Article  Google Scholar 

  14. Chen, S. Z.; Hou, Y. J.; Cheng, G.; Zhang, C. M.; Wang, S. X.; Zhang, J. C. Cerium oxide nanoparticles protect endothelial cells from apoptosis induced by oxidative stress. Biol. Trace Elem. Res. 2013, 154, 156–166.

    Article  Google Scholar 

  15. Dowding, J. M.; Das, S.; Kumar, A.; Dosani, T.; McCormack, R.; Gupta, A.; Sayle, T. X. T.; Sayle, D. C.; von Kalm, L.; Seal, S. et al. Cellular interaction and toxicity depend on physicochemical properties and surface modification of redox-active nanomaterials. ACS Nano 2013, 7, 4855–4868.

    Article  Google Scholar 

  16. Selvaraj, V.; Nepal, N.; Rogers, S.; Manne, N. D. P. K.; Arvapalli, R.; Rice, K. M.; Asano, S.; Fankhanel, E.; Ma, J. J.; Shokuhfar, T. et al. Inhibition of MAP kinase/NF-kB mediated signaling and attenuation of lipopolysaccharide induced severe sepsis by cerium oxide nanoparticles. Biomaterials 2015, 59, 160–171.

    Article  Google Scholar 

  17. Hirst, S. M.; Karakoti, A. S.; Tyler, R. D.; Sriranganathan, N.; Seal, S.; Reilly, C. M. Anti-inflammatory properties of cerium oxide nanoparticles. Small 2009, 5, 2848–2856.

    Article  Google Scholar 

  18. Manne, N. D.; Arvapalli, R.; Nepal, N.; Thulluri, S.; Selvaraj, V.; Shokuhfar, T.; He, K.; Rice, K. M.; Asano, S.; Maheshwari, M. et al. Therapeutic potential of cerium oxide nanoparticles for the treatment of peritonitis induced by polymicrobial insult in Sprague–Dawley rats. Crit. Care Med. 2015, 43, e477–e489.

    Article  Google Scholar 

  19. Manne, N. D. P. K.; Arvapalli, R.; Nepal, N.; Shokuhfar, T.; Rice, K. M.; Asano, S.; Blough, E. R. Cerium oxide nanoparticles attenuate acute kidney injury induced by intra-abdominal infection in Sprague–Dawley rats. J. Nanobiotechnology 2015, 13, 75.

    Article  Google Scholar 

  20. Kyosseva, S. V.; Chen, L. J.; Seal, S.; McGinnis, J. F. Nanoceria inhibit expression of genes associated with inflammation and angiogenesis in the retina of Vldlr null mice. Exp. Eye Res. 2013, 116, 63–74.

    Article  Google Scholar 

  21. Kim, C. K.; Kim, T.; Choi, I. Y.; Soh, M.; Kim, D.; Kim, Y. J.; Jang, H.; Yang, H. S.; Kim, J. Y.; Park, H. K. et al. Ceria nanoparticles that can protect against ischemic stroke. Angew. Chem., Int. Ed. 2012, 51, 11039–11043.

    Article  Google Scholar 

  22. Mracsko, E.; Veltkamp, R. Neuroinflammation after intracerebral hemorrhage. Front. Cell. Neurosci. 2014, 8, 388.

    Article  Google Scholar 

  23. Chao, C. C.; Hu, S. X.; Sheng, W. S.; Bu, D. F.; Bukrinsky, M. I.; Peterson, P. K. Cytokine-stimulated astrocytes damage human neurons via a nitric oxide mechanism. Glia 1996, 16, 276–284.

    Article  Google Scholar 

  24. Sinensky, M. C.; Leiser, A. L.; Babich, H. Oxidative stress aspects of the cytotoxicity of carbamide peroxide: In vitro studies. Toxicol. Lett. 1995, 75, 101–109.

    Article  Google Scholar 

  25. Grossetete, M.; Rosenberg, G. A. Matrix metalloproteinase inhibition facilitates cell death in intracerebral hemorrhage in mouse. J. Cereb. Blood Flow Metab. 2008, 28, 752–763.

    Article  Google Scholar 

  26. Aguilar, M. I.; Brott, T. G. Update in intracerebral hemorrhage. Neurohospitalist 2011, 1, 148–159.

    Article  Google Scholar 

  27. Kim, C. K.; Ryu, W. S.; Choi, I. Y.; Kim, Y. J.; Rim, D.; Kim, B. J.; Jang, H.; Yoon, B. W.; Lee, S. H. Detrimental effects of leptin on intracerebral hemorrhage via the STAT3 signal pathway. J. Cereb. Blood Flow Metab. 2013, 33, 944–953.

    Article  Google Scholar 

  28. Jung, K. H.; Chu, K.; Jeong, S. W.; Han, S. Y.; Lee, S. T.; Kim, J. Y.; Kim, M.; Roh, J. K. HMG-CoA reductase inhibitor, atorvastatin, promotes sensorimotor recovery, suppressing acute inflammatory reaction after experimental intracerebral hemorrhage. Stroke 2004, 35, 1744–1749.

    Article  Google Scholar 

  29. Huang, F.-P.; Xi, G. H.; Keep, R. F.; Hua, Y.; Nemoianu, A.; Hoff, J. T. Brain edema after experimental intracerebral hemorrhage: Role of hemoglobin degradation products. J. Neurosurg. 2002, 96, 287–293.

    Article  Google Scholar 

  30. Crow, J. P. Dichlorodihydrofluorescein and dihydrorhodamine 123 are sensitive indicators of peroxynitrite in vitro: Implications for intracellular measurement of reactive nitrogen and oxygen species. Nitric Oxide 1997, 1, 145–157.

    Article  Google Scholar 

  31. Grisham, M. B.; Jourd’Heuil, D.; Wink, D. A. Nitric oxide. I. Physiological chemistry of nitric oxide and its metabolites: Implications in inflammation. Am. J. Physiol. 1999, 276, G315–G321.

    Google Scholar 

  32. Laird, M. D.; Wakade, C.; Alleyne, C. H., Jr.; Dhandapani, K. M. Hemin-induced necroptosis involves glutathione depletion in mouse astrocytes. Free Radic. Biol. Med. 2008, 45, 1103–1114.

    Article  Google Scholar 

  33. Mitchell, J. A.; Warner, T. D. Cyclo-oxygenase-2: Pharmacology, physiology, biochemistry and relevance to NSAID therapy. Br. J. Pharmacol. 1999, 128, 1121–1132.

    Article  Google Scholar 

  34. Gavrieli, Y.; Sherman, Y.; Ben-Sasson, S. A. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J. Cell Biol. 1992, 119, 493–501.

    Article  Google Scholar 

  35. Ljosa, V.; Carpenter, A. E. Introduction to the quantitative analysis of two-dimensional fluorescence microscopy images for cell-based screening. PLoS Comput. Biol. 2009, 5, e1000603.

    Article  Google Scholar 

  36. MacLellan, C. L.; Silasi, G.; Poon, C. C.; Edmundson, C. L.; Buist, R.; Peeling, J.; Colbourne, F. Intracerebral hemorrhage models in rat: Comparing collagenase to blood infusion. J. Cereb. Blood Flow Metab. 2008, 28, 516–525.

    Article  Google Scholar 

  37. Karakoti, A. S.; Kuchibhatla, S. V. N. T.; Babu, K. S.; Seal, S. Direct synthesis of nanoceria in aqueous polyhydroxyl solutions. J. Phys. Chem. C 2007, 111, 17232–17240.

    Article  Google Scholar 

  38. Karakoti, A. S.; Monteiro-Riviere, N. A.; Aggarwal, R.; Davis, J. P.; Narayan, R. J.; Self, W. T.; McGinnis, J.; Seal, S. Nanoceria as antioxidant: Synthesis and biomedical applications. JOM 2008, 60, 33–37.

    Article  Google Scholar 

  39. Poma, A.; Ragnelli, A. M.; de Lapuente, J.; Ramos, D.; Borras, M.; Aimola, P.; Di Gioacchino, M.; Santucci, S.; De Marzi, L. In vivo inflammatory effects of ceria nanoparticles on CD-1 mouse: Evaluation by hematological, histological, and TEM analysis. J. Immunol. Res. 2014, 2014, 361419.

    Article  Google Scholar 

  40. Alili, L.; Sack, M.; von Montfort, C.; Giri, S.; Das, S.; Carroll, K. S.; Zanger, K.; Seal, S.; Brenneisen, P. Downregulation of tumor growth and invasion by redox-active nanoparticles. Antioxid. Redox Signal. 2013, 19, 765–778.

    Article  Google Scholar 

  41. Park, E.-J.; Choi, J.; Park, Y.-K.; Park, K. Oxidative stress induced by cerium oxide nanoparticles in cultured BEAS-2B cells. Toxicology 2008, 245, 90–100.

    Article  Google Scholar 

  42. Kazui, S.; Naritomi, H.; Yamamoto, H.; Sawada, T.; Yamaguchi, T. Enlargement of spontaneous intracerebral hemorrhage: Incidence and time course. Stroke 1996, 27, 1783–1787.

    Article  Google Scholar 

  43. Goldstein, L.; Teng, Z. P.; Zeserson, E.; Patel, M.; Regan, R. F. Hemin induces an iron-dependent, oxidative injury to human neuron-like cells. J Neurosci. Res. 2003, 73, 113–121.

    Article  Google Scholar 

  44. Wagner, K. R.; Sharp, F. R.; Ardizzone, T. D.; Lu, A. G.; Clark, J. F. Heme and iron metabolism: Role in cerebral hemorrhage. J. Cereb. Blood Flow Metab. 2003, 23, 629–652.

    Article  Google Scholar 

  45. Kress, G. J.; Dineley, K. E.; Reynolds, I. J. The relationship between intracellular free iron and cell injury in cultured neurons, astrocytes, and oligodendrocytes. J. Neurosci. 2002, 22, 5848–5855.

    Google Scholar 

  46. Barbieri, S. S.; Eligini, S.; Brambilla, M.; Tremoli, E.; Colli, S. Reactive oxygen species mediate cyclooxygenase-2 induction during monocyte to macrophage differentiation: Critical role of NADPH oxidase. Cardiovasc. Res. 2003, 60, 187–197.

    Article  Google Scholar 

  47. Campuzano, O.; Castillo-Ruiz, M. M.; Acarin, L.; Castellano, B.; Gonzalez, B. Distinct pattern of microglial response, cyclooxygenase-2, and inducible nitric oxide synthase expression in the aged rat brain after excitotoxic damage. J. Neurosci. Res. 2008, 86, 3170–3183.

    Article  Google Scholar 

  48. Meyer, M.; Schreck, R.; Baeuerle, P. A. H2O2 and antioxidants have opposite effects on activation of NF-kappa B and AP-1 in intact cells: AP-1 as secondary antioxidant-responsive factor. EMBO J. 1993, 12, 2005–2015.

    Google Scholar 

  49. Ding, R.; Chen, Y. Z.; Yang, S.; Deng, X. Q.; Fu, Z. H.; Feng, L.; Cai, Y. Q.; Du, M. X.; Zhou, Y. X.; Tang, Y. P. Blood-brain barrier disruption induced by hemoglobin in vivo: Involvement of up-regulation of nitric oxide synthase and peroxynitrite formation. Brain Res. 2014, 1571, 25–38.

    Article  Google Scholar 

  50. Wagner, K. R.; Packard, B. A.; Hall, C. L.; Smulian, A. G.; Linke, M. J.; de Courten-Myers, G. M.; Packard, L. M.; Hall, N. C. Protein oxidation and heme oxygenase-1 induction in porcine white matter following intracerebral infusions of whole blood or plasma. Dev. Neurosci. 2002, 24, 154–160.

    Article  Google Scholar 

  51. Mittal, M.; Siddiqui, M. R.; Tran, K.; Reddy, S. P.; Malik, A. B. Reactive oxygen species in inflammation and tissue injury. Antioxid. Redox Sign. 2014, 20, 1126–1167.

    Article  Google Scholar 

  52. Selvaraj, V.; Manne, N. D.; Arvapalli, R.; Rice, K. M.; Nandyala, G.; Fankenhanel, E.; Blough, E. R. Effect of cerium oxide nanoparticles on sepsis induced mortality and NF-?B signaling in cultured macrophages. Nanomedicine 2015, 10, 1275–1288.

    Article  Google Scholar 

  53. Hu, X.; Tao, C. Y.; Gan, Q.; Zheng, J.; Li, H.; You, C. Oxidative stress in intracerebral hemorrhage: Sources, mechanisms, and therapeutic targets. Oxid. Med. Cell. Longev. 2016, 2016, 3215391.

    Google Scholar 

  54. Zhao, X. R.; Song, S.; Sun, G. H.; Strong, R.; Zhang, J.; Grotta, J. C.; Aronowski, J. Neuroprotective role of haptoglobin after intracerebral hemorrhage. J. Neurosci. 2009, 29, 15819–15827.

    Article  Google Scholar 

  55. Nakamura, T.; Keep, R. F.; Hua, Y.; Schallert, T.; Hoff, J. T.; Xi, G. H. Deferoxamine-induced attenuation of brain edema and neurological deficits in a rat model of intracerebral hemorrhage. J. Neurosurg. 2004, 100, 672–678.

    Article  Google Scholar 

  56. Lin, S.; Yin, Q.; Zhong, Q.; Lv, F.-L.; Zhou, Y.; Li, J.-Q.; Wang, J.-Z.; Su, B. Y.; Yang, Q.-W. Heme activates TLR4- mediated inflammatory injury via MyD88/TRIF signaling pathway in intracerebral hemorrhage. J. Neuroinflamm. 2012, 9, 46.

    Google Scholar 

  57. Gong, C.; Ennis, S. R.; Hoff, J. T.; Keep, R. F. Inducible cyclooxygenase-2 expression after experimental intracerebral hemorrhage. Brain Res. 2001, 901, 38–46.

    Article  Google Scholar 

  58. Wu, B.; Chen, X. H.; He, B.; Liu, S. Y.; Li, Y. F.; Wang, Q. X.; Gao, H. J.; Wang, S. F.; Liu, J. B.; Zhang, S. C. et al. ROS are critical for endometrial breakdown via NF-κB–COX-2 signaling in a female mouse menstrual-like model. Endocrinology 2014, 155, 3638–3648.

    Article  Google Scholar 

  59. Zhao, X. R.; Zhang, Y. J.; Strong, R.; Zhang, J.; Grotta, J. C.; Aronowski, J. Distinct patterns of intracerebral hemorrhageinduced alterations in NF-?B subunit, iNOS, and COX-2 expression. J. Neurochem. 2007, 101, 652–663.

    Article  Google Scholar 

  60. Taylor, R. A.; Sansing, L. H. Microglial responses after ischemic stroke and intracerebral hemorrhage. Clin. Dev. Immunol. 2013, 2013, 746068.

    Article  Google Scholar 

  61. Fortes, G. B.; Alves, L. S.; de Oliveira, R.; Dutra, F. F.; Rodrigues, D.; Fernandez, P. L.; Souto-Padron, T.; De Rosa, M. J.; Kelliher, M.; Golenbock, D. et al. Heme induces programmed necrosis on macrophages through autocrine TNF and ROS production. Blood 2012, 119, 2368–2375.

    Article  Google Scholar 

  62. Fleury, C.; Mignotte, B.; Vayssière, J.-L. Mitochondrial reactive oxygen species in cell death signaling. Biochimie 2002, 84, 131–141.

    Article  Google Scholar 

  63. Orrenius, S. Reactive oxygen species in mitochondriamediated cell death. Drug Metab. Rev. 2007, 39, 443–455.

    Article  Google Scholar 

  64. Bergsbaken, T.; Fink, S. L.; Cookson, B. T. Pyroptosis: Host cell death and inflammation. Nat. Rev. Microbiol. 2009, 7, 99–109.

    Article  Google Scholar 

  65. Lockman, P. R.; Mumper, R. J.; Khan, M. A.; Allen, D. D. Nanoparticle technology for drug delivery across the bloodbrain barrier. Drug Dev. Ind. Pharm. 2002, 28, 1–13.

    Article  Google Scholar 

  66. Wang, J. Preclinical and clinical research on inflammation after intracerebral hemorrhage. Prog. Neurobiol. 2010, 92, 463–477.

    Article  Google Scholar 

  67. Dahnovici, R. M.; Pintea, I. L.; Malaescu, D. G.; Busuioc, C. J.; Predescu, A.; Mogoanta, L. Microscopic aspects of macrophage system cells in hemorrhagic stroke in humans. Rom. J. Morphol. Embryol. 2011, 52, 1249–1253.

    Google Scholar 

  68. Chu, K.; Jeong, S. W.; Jung, K. H.; Han, S. Y.; Lee, S. T.; Kim, M.; Roh, J. K. Celecoxib induces functional recovery after intracerebral hemorrhage with reduction of brain edema and perihematomal cell death. J. Cereb. Blood Flow Metab. 2004, 24, 926–933.

    Article  Google Scholar 

  69. Xi, G. H.; Wagner, K. R.; Keep, R. F.; Hua, Y.; de Courten-Myers, G. M.; Broderick, J. P.; Brott, T. G.; Hoff, J. T.; Muizelaar, J. P. Role of blood clot formation on early edema development after experimental intracerebral hemorrhage. Stroke 1998, 29, 2580–2586.

    Article  Google Scholar 

  70. Xi, G. H.; Reiser, G.; Keep, R. F. The role of thrombin and thrombin receptors in ischemic, hemorrhagic and traumatic brain injury: Deleterious or protective? J. Neurochem. 2003, 84, 3–9.

    Article  Google Scholar 

  71. Wu, H.; Wu, T.; Xu, X. Y.; Wang, J.; Wang, J. Iron toxicity in mice with collagenase-induced intracerebral hemorrhage. J. Cereb. Blood Flow Metab. 2011, 31, 1243–1250.

    Article  Google Scholar 

  72. Sykora, M.; Diedler, J.; Turcani, P.; Rupp, A.; Steiner, T. Subacute perihematomal edema in intracerebral hemorrhage is associated with impaired blood pressure regulation. J. Neurol. Sci. 2009, 284, 108–112.

    Article  Google Scholar 

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Acknowledgements

This work was supported by grants of the followings: The Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), the Ministry of Health & Welfare, Republic of Korea (No. HI14C0211), Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (No. NRF-2015R1A2A2A 01007770), and the Institute for Basic Science (IBS), Republic of Korea (No. IBS-R006-D1).

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Authors and Affiliations

  1. Laboratory of Innovative Nanobiotechnology, Biomedical Research Institute, Seoul National University Hospital, Seoul, 03080, Republic of Korea

    Dong-Wan Kang, Chi Kyung Kim, Han-Gil Jeong, In-Young Choi, Seul-Ki Ki, Do Yeon Kim, Wookjin Yang & Seung-Hoon Lee

  2. Department of Neurology, Seoul National University Hospital, Seoul, 03080, Republic of Korea

    Dong-Wan Kang, Han-Gil Jeong, In-Young Choi, Seul-Ki Ki, Do Yeon Kim, Wookjin Yang & Seung-Hoon Lee

  3. Department of Neurology, Korea University Guro Hospital and Korea University College of Medicine, Seoul, 08308, Republic of Korea

    Chi Kyung Kim

  4. Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul, 151-742, Republic of Korea

    Min Soh, Taeho Kim & Taeghwan Hyeon

  5. School of Chemical and Biological Engineering and Institute of Chemical Processes, Seoul National University, Seoul, 151-742, Republic of Korea

    Min Soh, Taeho Kim & Taeghwan Hyeon

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  1. Dong-Wan Kang
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Biocompatible custom ceria nanoparticles against reactive oxygen species resolve acute inflammatory reaction after intracerebral hemorrhage

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Kang, DW., Kim, C.K., Jeong, HG. et al. Biocompatible custom ceria nanoparticles against reactive oxygen species resolve acute inflammatory reaction after intracerebral hemorrhage. Nano Res. 10, 2743–2760 (2017). https://doi.org/10.1007/s12274-017-1478-6

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