Journal Home > Volume 11 , Issue 7
Nano Research 2018, 11(7): 3582-3592 https://doi.org/10.1007/s12274-017-1924-5
Research Article | Issue | Published: 02 August 2018

Customized lipid-coated magnetic mesoporous silica nanoparticle doped with ceria nanoparticles for theragnosis of intracerebral hemorrhage

Show Author's Information Bong Geun Cha1,§,  Han-Gil Jeong2,3,§,  Dong-Wan Kang2,3,  Myong-Joo Nam1,  Chi Kyung Kim2,4,  Do Yeon Kim2,3,  In-Young Choi2,3,  Seul Ki Ki2,3,  Song I. Kim2,3,  Ju hee Han2,3,  Jaeyun Kim1,5,6( ),  Seung-Hoon Lee2,3( )
School of Chemical EngineeringSungkyunkwan UniversitySuwon16419Republic of Korea
Department of Laboratory of Innovative NanobiotechnologyBiomedical Research InstituteSeoul National University Hospital 101Daehak-roJongno-guSeoul03080Republic of Korea
Department of NeurologySeoul National University Hospital 101Daehak-roJongno-guSeoul03080Republic of Korea
Department of NeurologyKorea University Guro Hospital and Korea University College of MedicineSeoul08308Republic of Korea
Department of Health Sciences and TechnologySamsung Advanced Institute for Health Science & Technology (SAIHST)Sungkyunkwan UniversitySuwon16419Republic of Korea
Biomedical Institute for Convergence at SKKU (BICS)Sungkyunkwan University (SKKU)Suwon16419Republic of Korea

§Bong Geun Cha and Han-Gil Jeong contributed equally to this work.

Keywords:
imaging, therapeutics, reactive oxygen species, intracerebral hemorrhage, magnetic mesoporous silica nanoparticle, ceria nanoparticles
Cite this article:
Cha BG, Jeong H-G, Kang D-W, et al. Customized lipid-coated magnetic mesoporous silica nanoparticle doped with ceria nanoparticles for theragnosis of intracerebral hemorrhage. Nano Research, 2018, 11(7): 3582-3592. https://doi.org/10.1007/s12274-017-1924-5
Download citation
EndNote(RIS)
BibTeX

547

Views

21

Downloads

Citations

33

Crossref

N/A

WoS

32

Scopus

0

CSCD

Abstract Full text Electronic supplementary material About this article

Intracerebral hemorrhage (ICH), caused by the sudden rupture of an artery within the brain, is a devastating subtype of stroke, which currently has no effective treatment. Intense inflammatory reactions that occur in the peri-hematomal area after ICH are more deleterious than the hematoma itself, resulting in subsequent brain edema and neurologic deterioration. Thus, we developed lipid-coated magnetic mesoporous silica nanoparticles doped with ceria nanoparticles (CeNPs), abbreviated as LMCs, which have both potent anti-inflammatory therapeutic effects via scavenging reactive oxygen species and help in increasing the efficacy of magnetic resonance imaging enhancement in the peri-hematomal area. LMCs consist of mesoporous silica nanoparticle-supported lipid bilayers, which are loaded with large amounts of CeNPs for scavenging of reactive oxygen species, and iron oxide nanoparticles for magnetic resonance imaging contrast. LMCs loaded with CeNPs exhibited strong anti-oxidative and anti-inflammatory activities in vitro. In the rodent ICH model, intracerebrally injected LMCs reached the peri-hematomal area and were engulfed by macrophages, which were clearly visualized by magnetic resonance imaging of the brain. Moreover, LMCs reduced inflammatory macrophage infiltration, and thus significantly reduced brain edema. Finally, LMC treatment markedly improved neurologic outcomes of the animals with ICH. Thus, LMC is the first nanobiomaterial that successfully showed theragnostic effects in ICH.


menu
Abstract
Full text
Outline
Electronic supplementary material
About this article

Customized lipid-coated magnetic mesoporous silica nanoparticle doped with ceria nanoparticles for theragnosis of intracerebral hemorrhage

Show Author's information Bong Geun Cha1,§, Han-Gil Jeong2,3,§, Dong-Wan Kang2,3, Myong-Joo Nam1, Chi Kyung Kim2,4, Do Yeon Kim2,3, In-Young Choi2,3, Seul Ki Ki2,3, Song I. Kim2,3, Ju hee Han2,3, Jaeyun Kim1,5,6( ), Seung-Hoon Lee2,3( )
School of Chemical EngineeringSungkyunkwan UniversitySuwon16419Republic of Korea
Department of Laboratory of Innovative NanobiotechnologyBiomedical Research InstituteSeoul National University Hospital 101Daehak-roJongno-guSeoul03080Republic of Korea
Department of NeurologySeoul National University Hospital 101Daehak-roJongno-guSeoul03080Republic of Korea
Department of NeurologyKorea University Guro Hospital and Korea University College of MedicineSeoul08308Republic of Korea
Department of Health Sciences and TechnologySamsung Advanced Institute for Health Science & Technology (SAIHST)Sungkyunkwan UniversitySuwon16419Republic of Korea
Biomedical Institute for Convergence at SKKU (BICS)Sungkyunkwan University (SKKU)Suwon16419Republic of Korea

§Bong Geun Cha and Han-Gil Jeong contributed equally to this work.

Abstract

Intracerebral hemorrhage (ICH), caused by the sudden rupture of an artery within the brain, is a devastating subtype of stroke, which currently has no effective treatment. Intense inflammatory reactions that occur in the peri-hematomal area after ICH are more deleterious than the hematoma itself, resulting in subsequent brain edema and neurologic deterioration. Thus, we developed lipid-coated magnetic mesoporous silica nanoparticles doped with ceria nanoparticles (CeNPs), abbreviated as LMCs, which have both potent anti-inflammatory therapeutic effects via scavenging reactive oxygen species and help in increasing the efficacy of magnetic resonance imaging enhancement in the peri-hematomal area. LMCs consist of mesoporous silica nanoparticle-supported lipid bilayers, which are loaded with large amounts of CeNPs for scavenging of reactive oxygen species, and iron oxide nanoparticles for magnetic resonance imaging contrast. LMCs loaded with CeNPs exhibited strong anti-oxidative and anti-inflammatory activities in vitro. In the rodent ICH model, intracerebrally injected LMCs reached the peri-hematomal area and were engulfed by macrophages, which were clearly visualized by magnetic resonance imaging of the brain. Moreover, LMCs reduced inflammatory macrophage infiltration, and thus significantly reduced brain edema. Finally, LMC treatment markedly improved neurologic outcomes of the animals with ICH. Thus, LMC is the first nanobiomaterial that successfully showed theragnostic effects in ICH.

Keywords: imaging, therapeutics, reactive oxygen species, intracerebral hemorrhage, magnetic mesoporous silica nanoparticle, ceria nanoparticles

References(37)

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.
DOI 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.
DOI Google Scholar
3

Balami, J. S. ; Buchan, A. M. Complications of intracerebral haemorrhage. Lancet Neurol. 2012, 11, 101–118.
DOI Google Scholar
4

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. STICH investigators. 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.
DOI Google Scholar
5

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.
DOI Google Scholar
6

Wang, J. ; Doré, S. Inflammation after intracerebral hemorrhage. J. Cerebr. Blood Flow Met. 2007, 27, 894–908.
DOI Google Scholar
7

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.
DOI Google Scholar
8

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.
DOI Google Scholar
9

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.
DOI Google Scholar
10

Nakamura, T. ; Keep, R. F. ; Hua, Y. ; Hoff, J. T. ; Xi, G. H. Oxidative DNA injury after experimental intracerebral hemorrhage. Brain Res. 2005, 1039, 30–36.
DOI Google Scholar
11

Katsu, M. ; Niizuma, K. ; Yoshioka, H. ; Okami, N. ; Sakata, H. ; Chan, P. H. Hemoglobin-induced oxidative stress contributes to matrix metalloproteinase activation and blood–brain barrier dysfunction in vivo. J. Cerebr. Blood Flow Met. 2010, 30, 1939–1950.
DOI Google Scholar
12

Wu, J. M. ; Hua, Y. ; Keep, R. F. ; Schallert, T. ; Hoff, J. T. ; Xi, G. H. Oxidative brain injury from extravasated erythrocytes after intracerebral hemorrhage. Brain Res. 2002, 953, 45–52.
DOI Google Scholar
13

Liu, K. J. ; Rosenberg, G. A. Matrix metalloproteinases and free radicals in cerebral ischemia. Free Rad. Biol. Med. 2005, 39, 71–80.
DOI Google Scholar
14

Lyden, P. D. ; Shuaib, A. ; Lees, K. R. ; Davalos, A. ; Davis, S. M. ; Diener, H. C. ; Grotta, J. C. ; Ashwood, T. J. ; Hardemark, H. G. ; Svensson, H. H. et al. Safety and tolerability of NXY-059 for acute intracerebral hemorrhage: The CHANT Trial. Stroke 2007, 38, 2262–2269.
DOI Google Scholar
15

Celardo, I. ; Pedersen, J. Z. ; Traversa, E. ; Ghibelli, L. Pharmacological potential of cerium oxide nanoparticles. Nanoscale 2011, 3, 1411–1420.
DOI Google Scholar
16

Pirmohamed, T. ; Dowding, J. M. ; Singh, S. ; Wasserman, B. ; Heckert, E. ; Karakoti, A. S. ; King, J. E. ; Seal, S. ; Self, W. T. Nanoceria exhibit redox state-dependent catalase mimetic activity. Chem. Commun. 2010, 46, 2736–2738.
DOI Google Scholar
17

Singh, S. ; Dosani, T. ; Karakoti, A. S. ; Kumar, A. ; Seal, S. ; Self, W. T. A phosphate-dependent shift in redox state of cerium oxide nanoparticles and its effects on catalytic properties. Biomaterials 2011, 32, 6745–6753.
DOI Google Scholar
18

Xu, C. ; Qu, X. G. Cerium oxide nanoparticle: A remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Mater. 2014, 6, e90.
DOI Google Scholar
19

Deshpande, S. ; Patil, S. ; Kuchibhatla, S. V. ; Seal, S. Size dependency variation in lattice parameter and valency states in nanocrystalline cerium oxide. Appl. Phys. Lett. 2005, 87, 133113.
DOI Google Scholar
20

Korsvik, C. ; Patil, S. ; Seal, S. ; Self, W. T. Superoxide dismutase mimetic properties exhibited by vacancy engineered ceria nanoparticles. Chem. Commun. 2007, 1056–1058.
DOI Google Scholar
21

Heckert, E. G. ; Karakoti, A. S. ; Seal, S. ; Self, W. T. The role of cerium redox state in the SOD mimetic activity of nanoceria. Biomaterials 2008, 29, 2705–2709.
DOI Google Scholar
22

Celardo, I. ; De Nicola, M. ; Mandoli, C. ; Pedersen, J. Z. ; Traversa, E. ; Ghibelli, L. Ce3+ ions determine redox-dependent anti-apoptotic effect of cerium oxide nanoparticles. ACS Nano 2011, 5, 4537–4549.
DOI Google Scholar
23

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.
DOI Google Scholar
24

Cimini, A. ; D' Angelo, B. ; Das, S. ; Gentile, R. ; Benedetti, E. ; Singh, V. ; Monaco, A. M. ; Santucci, S. ; Seal, S. Antibodyconjugated PEGylated cerium oxide nanoparticles for specific targeting of Aβ aggregates modulate neuronal survival pathways. Acta Biomater. 2012, 8, 2056–2067.
DOI Google Scholar
25

Lu, J. ; Liong, M. ; Li, Z. X. ; Zink, J. I. ; Tamanoi, F. Biocompatibility, biodistribution, and drug-delivery efficiency of mesoporous silica nanoparticles for cancer therapy in animals. Small 2010, 6, 1794–1805.
DOI Google Scholar
26

Trewyn, B. G. ; Slowing, I. I. ; Giri, S. ; Chen, H. T. ; Lin, V. S. Y. Synthesis and functionalization of a mesoporous silica nanoparticle based on the sol–gel process and applications in controlled release. Acc. Chem. Res. 2007, 40, 846–853.
DOI Google Scholar
27

Tang, F. Q. ; Li, L. L. ; Chen, D. Mesoporous silica nanoparticles: Synthesis, biocompatibility and drug delivery. Adv. Mater. 2012, 24, 1504–1534.
DOI Google Scholar
28

Ashley, C. E. ; Carnes, E. C. ; Phillips, G. K. ; Padilla, D. ; Durfee, P. N. ; Brown, P. A. ; Hanna, T. N. ; Liu, J. W. ; Phillips, B. ; Carter, M. B. et al. The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers. Nat. Mater. 2011, 10, 389–397.
DOI Google Scholar
29

Kim, J. ; Kim, H. S. ; Lee, N. ; Kim, T. ; Kim, H. ; Yu, T. ; Song, I. C. ; Moon, W. K. ; Hyeon, T. Multifunctional uniform nanoparticles composed of a magnetite nanocrystal core and a mesoporous silica shell for magnetic resonance and fluorescence imaging and for drug delivery. Angew. Chem., Int. Ed. 2008, 47, 8438–8441.
DOI Google Scholar
30

Yu, T. ; Lim, B. ; Xia, Y. N. Aqueous-phase synthesis of single-crystal ceria nanosheets. Angew. Chem., Int. Ed. 2010, 49, 4484–4487.
DOI Google Scholar
31

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.
DOI Google Scholar
32

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. Cerebr. Blood Flow Met. 2008, 28, 516–525.
DOI Google Scholar
33

Kang, D. W. ; Kim, C. K. ; Jeong, H. G. ; Soh, M. ; Kim, T. ; Choi, I. Y. ; Ki, S. K. ; Kim, D. Y. ; Yang, W. ; Hyeon, T. et al. Biocompatible custom ceria nanoparticles against reactive oxygen species resolve acute inflammatory reaction after intracerebral hemorrhage. Nano Res. 2017, 10, 2743–2760.
DOI Google Scholar
34

Keep, R. F. ; Hua, Y. ; Xi, G. H. Brain water content: A misunderstood measurement? Transl. Stroke Res. 2012, 3, 263–265.
DOI Google Scholar
35

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.
DOI Google Scholar
36

Hua, Y. ; Schallert, T. ; Keep, R. F. ; Wu, J. M. ; Hoff, J. T. ; Xi, G. H. Behavioral tests after intracerebral hemorrhage in the rat. Stroke 2002, 33, 2478–2484.
DOI Google Scholar
37

Xi, G. H. ; Hua, Y. ; Bhasin, R. R. ; Ennis, S. R. ; Keep, R. F. ; Hoff, J. T. Mechanisms of edema formation after intracerebral hemorrhage: Effects of extravasated red blood cells on blood flow and blood-brain barrier integrity. Stroke 2001, 32, 2932–2938.
DOI Google Scholar
File
12274_2017_1924_MOESM1_ESM.pdf (638 KB)
Publication history
Copyright
Acknowledgements

Publication history

Received: 26 September 2017
Revised: 12 November 2017
Accepted: 14 November 2017
Published: 02 August 2018
Issue date: July 2018

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2017

Acknowledgements

Acknowledgements

This research was supported by a grant of the Korea Health Technology R & D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (No. HI17C0076), and also supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (No. NRF-2015R1A2A2A01007770).

Return