Absence of cytotoxicity towards microglia of iron oxide (α-Fe2O3) nanorhombohedra
Abstract
Understanding the nature of interactions between nanomaterials, such as commercially ubiquitous hematite (α-Fe2O3) nanorhombohedra (N-Rhomb) and biological systems is of critical importance for gaining insight into the practical applicability of nanomaterials. Microglia represent the first line of defense in the central nervous system (CNS) during severe injury or disease such as Parkinson's and Alzheimer's disease as illustrative examples. Hence, to analyze the potential cytotoxic effect of N-Rhomb exposure in the presence of microglia, we have synthesized Rhodamine B (RhB)-labeled α-Fe2O3 N-Rhomb, with lengths of 47 ± 10 nm and widths of 35 ± 8 nm. Internalization of RhB-labeled α-Fe2O3 N-Rhomb by microglia in the mouse brain was observed, and a dose-dependent increase in the cellular iron content as probed by cellular fluorescence was detected in cultured microglia after nanoparticle exposure. The cells maintained clear functional viability, exhibiting little to no cytotoxic effects after 24 and 48 hours at acceptable, physiological concentrations. Importantly, the nanoparticle exposure did not induce microglial cells to produce either tumor necrosis factor alpha (TNFα) or interleukin 1-beta (IL1β), two pro-inflammatory cytokines, nor did exposure stimulate the production of nitrites and reactive oxygen species (ROS), which are common indicators for the onset of inflammation. Finally, we proposemore »
- Authors:
-
- Department of Chemistry, State University of New York at Stony Brook, Stony Brook, New York 11794-3400, USA
- Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, New York 11794-8651, USA
- Department of Chemistry, State University of New York at Stony Brook, Stony Brook, New York 11794-3400, USA, Condensed Matter Physics and Materials Science Department, Building 480, Brookhaven National Laboratory, Upton, New York 11973, USA
- Publication Date:
- Research Org.:
- Brookhaven National Laboratory (BNL), Upton, NY (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1603375
- Alternate Identifier(s):
- OSTI ID: 1240707
- Report Number(s):
- BNL-111876-2016-JA
Journal ID: ISSN 2045-4538
- Grant/Contract Number:
- SC-00112704; SC00112704
- Resource Type:
- Published Article
- Journal Name:
- Toxicology Research (Online)
- Additional Journal Information:
- Journal Name: Toxicology Research (Online) Journal Volume: 5 Journal Issue: 3; Journal ID: ISSN 2045-4538
- Publisher:
- Oxford University Press
- Country of Publication:
- United Kingdom
- Language:
- English
- Subject:
- 75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; α-Fe2O3; nanostructures; microglia; cytotoxicity; neurotoxicity
Citation Formats
Lewis, Crystal S., Torres, Luisa, Miyauchi, Jeremy T., Rastegar, Cyrus, Patete, Jonathan M., Smith, Jacqueline M., Wong, Stanislaus S., and Tsirka, Stella E. Absence of cytotoxicity towards microglia of iron oxide (α-Fe2O3) nanorhombohedra. United Kingdom: N. p., 2016.
Web. doi:10.1039/c5tx00421g.
Lewis, Crystal S., Torres, Luisa, Miyauchi, Jeremy T., Rastegar, Cyrus, Patete, Jonathan M., Smith, Jacqueline M., Wong, Stanislaus S., & Tsirka, Stella E. Absence of cytotoxicity towards microglia of iron oxide (α-Fe2O3) nanorhombohedra. United Kingdom. https://doi.org/10.1039/c5tx00421g
Lewis, Crystal S., Torres, Luisa, Miyauchi, Jeremy T., Rastegar, Cyrus, Patete, Jonathan M., Smith, Jacqueline M., Wong, Stanislaus S., and Tsirka, Stella E. Fri .
"Absence of cytotoxicity towards microglia of iron oxide (α-Fe2O3) nanorhombohedra". United Kingdom. https://doi.org/10.1039/c5tx00421g.
@article{osti_1603375,
title = {Absence of cytotoxicity towards microglia of iron oxide (α-Fe2O3) nanorhombohedra},
author = {Lewis, Crystal S. and Torres, Luisa and Miyauchi, Jeremy T. and Rastegar, Cyrus and Patete, Jonathan M. and Smith, Jacqueline M. and Wong, Stanislaus S. and Tsirka, Stella E.},
abstractNote = {Understanding the nature of interactions between nanomaterials, such as commercially ubiquitous hematite (α-Fe2O3) nanorhombohedra (N-Rhomb) and biological systems is of critical importance for gaining insight into the practical applicability of nanomaterials. Microglia represent the first line of defense in the central nervous system (CNS) during severe injury or disease such as Parkinson's and Alzheimer's disease as illustrative examples. Hence, to analyze the potential cytotoxic effect of N-Rhomb exposure in the presence of microglia, we have synthesized Rhodamine B (RhB)-labeled α-Fe2O3 N-Rhomb, with lengths of 47 ± 10 nm and widths of 35 ± 8 nm. Internalization of RhB-labeled α-Fe2O3 N-Rhomb by microglia in the mouse brain was observed, and a dose-dependent increase in the cellular iron content as probed by cellular fluorescence was detected in cultured microglia after nanoparticle exposure. The cells maintained clear functional viability, exhibiting little to no cytotoxic effects after 24 and 48 hours at acceptable, physiological concentrations. Importantly, the nanoparticle exposure did not induce microglial cells to produce either tumor necrosis factor alpha (TNFα) or interleukin 1-beta (IL1β), two pro-inflammatory cytokines, nor did exposure stimulate the production of nitrites and reactive oxygen species (ROS), which are common indicators for the onset of inflammation. Finally, we propose that under the conditions of our experiments, i.e. in the presence of RhB labeled-α-Fe2O3 N-Rhomb maintaining concentrations of up to 100 μg mL–1 after 48 hours of incubation, the in vitro and in vivo internalization of RhB-labeled α-Fe2O3 N-Rhomb are likely to be clathrin-dependent, which represents a conventional mechanistic uptake route for most cells. Furthermore, given the crucial role that microglia play in many neurological disorders, understanding the potential cytotoxic effects of these nanostructures is of fundamental importance if they are to be used in a therapeutic setting.},
doi = {10.1039/c5tx00421g},
journal = {Toxicology Research (Online)},
number = 3,
volume = 5,
place = {United Kingdom},
year = {Fri Feb 26 00:00:00 EST 2016},
month = {Fri Feb 26 00:00:00 EST 2016}
}
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1039/c5tx00421g
https://doi.org/10.1039/c5tx00421g
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 7 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Microglial activation, recruitment and phagocytosis as linked phenomena in ferric oxide nanoparticle exposure
journal, August 2011
- Wang, Yun; Wang, Bing; Zhu, Mo-Tao
- Toxicology Letters, Vol. 205, Issue 1
Tuftsin signals through its receptor neuropilin-1 via the transforming growth factor beta pathway
journal, September 2013
- Nissen, Jillian C.; Selwood, David L.; Tsirka, Stella E.
- Journal of Neurochemistry, Vol. 127, Issue 3
Features of Microglia and Neuroinflammation Relevant to Environmental Exposure and Neurotoxicity
journal, July 2011
- Kraft, Andrew D.; Harry, G. Jean
- International Journal of Environmental Research and Public Health, Vol. 8, Issue 7
Tubby regulates microglial phagocytosis through MerTK
journal, November 2012
- Caberoy, Nora B.; Alvarado, Gabriela; Li, Wei
- Journal of Neuroimmunology, Vol. 252, Issue 1-2
Regulation of tumour necrosis factor signalling: live or let die
journal, May 2015
- Brenner, Dirk; Blaser, Heiko; Mak, Tak W.
- Nature Reviews Immunology, Vol. 15, Issue 6
Biocompatibility and Delivery of NGF by Hematite Nanotubes for Differentiation of PC12 Cells
journal, November 2010
- Chen, Linfeng; Xie, Jining; Yancey, J.
- Journal of Nanotechnology in Engineering and Medicine, Vol. 1, Issue 4
Nanotechnology, nanotoxicology, and neuroscience
journal, February 2009
- Suh, Won Hyuk; Suslick, Kenneth S.; Stucky, Galen D.
- Progress in Neurobiology, Vol. 87, Issue 3
Minocycline selectively inhibits M1 polarization of microglia
journal, March 2013
- Kobayashi, K.; Imagama, S.; Ohgomori, T.
- Cell Death & Disease, Vol. 4, Issue 3
Internalization of Carbon Black and Maghemite Iron Oxide Nanoparticle Mixtures Leads to Oxidant Production
journal, December 2010
- Berg, J. Michael; Ho, Shu; Hwang, Wonjoong
- Chemical Research in Toxicology, Vol. 23, Issue 12
Endocytotic uptake of iron oxide nanoparticles by cultured brain microglial cells
journal, September 2013
- Luther, Eva M.; Petters, Charlotte; Bulcke, Felix
- Acta Biomaterialia, Vol. 9, Issue 9
Mouse neutrophilic granulocytes express mRNA encoding the macrophage colony-stimulating factor receptor (CSF-1R) as well as many other macrophage-specific transcripts and can transdifferentiate into macrophages in vitro in response to CSF-1
journal, April 2007
- Sasmono, R. T.; Ehrnsperger, A.; Cronau, S. L.
- Journal of Leukocyte Biology, Vol. 82, Issue 1
Mechanisms of damage to myelin and oligodendrocytes and their relevance to disease
journal, December 1999
- Merrill, Scolding
- Neuropathology and Applied Neurobiology, Vol. 25, Issue 6, p. 435-458
The TNF and TNF Receptor Superfamilies
journal, February 2001
- Locksley, Richard M.; Killeen, Nigel; Lenardo, Michael J.
- Cell, Vol. 104, Issue 4
Superparamagnetic iron oxide nanoparticles (SPIONs): Development, surface modification and applications in chemotherapy
journal, January 2011
- Mahmoudi, Morteza; Sant, Shilpa; Wang, Ben
- Advanced Drug Delivery Reviews, Vol. 63, Issue 1-2, p. 24-46
Synthesis of cubic LiNbO3 nanoparticles and their application in vitro bioimaging
journal, September 2014
- Wang, Y.; Zhou, X. Y.; Chen, Z.
- Applied Physics A, Vol. 117, Issue 4
Polymeric nanoparticle system to target activated microglia/macrophages in spinal cord injury
journal, January 2014
- Papa, Simonetta; Ferrari, Raffaele; De Paola, Massimiliano
- Journal of Controlled Release, Vol. 174
Magnetic targeting for site-specific drug delivery: applications and clinical potential
journal, January 2009
- Polyak, Boris; Friedman, Gary
- Expert Opinion on Drug Delivery, Vol. 6, Issue 1
Inflammatory stress response in A549 cells as a result of exposure to coal: Evidence for the role of pyrite in coal workers’ pneumoconiosis pathogenesis
journal, October 2013
- Harrington, Andrea D.; Tsirka, Stella E.; Schoonen, Martin A. A.
- Chemosphere, Vol. 93, Issue 6
Neurotoxicity of low-dose repeatedly intranasal instillation of nano- and submicron-sized ferric oxide particles in mice
journal, June 2008
- Wang, Bing; Feng, Weiyue; Zhu, Motao
- Journal of Nanoparticle Research, Vol. 11, Issue 1
Brain uptake of thiamine-coated nanoparticles
journal, December 2003
- Lockman, Paul R.; Oyewumi, Moses O.; Koziara, Joanna M.
- Journal of Controlled Release, Vol. 93, Issue 3
Oligodendroglial Alterations and the Role of Microglia in White Matter Injury: Relevance to Schizophrenia
journal, January 2013
- Chew, Li-Jin; Fusar-Poli, Paolo; Schmitz, Thomas
- Developmental Neuroscience, Vol. 35, Issue 2-3
Cellular Toxicity of TiO2 Nanoparticles in Anatase and Rutile Crystal Phase
journal, May 2010
- Jin, Chan; Tang, Ying; Yang, F. Guang
- Biological Trace Element Research, Vol. 141, Issue 1-3
Evaluating Cytotoxicity and Cellular Uptake from the Presence of Variously Processed TiO 2 Nanostructured Morphologies
journal, May 2010
- Chen, Jingyi; Zhou, Hongjun; Santulli, Alexander C.
- Chemical Research in Toxicology, Vol. 23, Issue 5
The Classification of Microglial Activation Phenotypes on Neurodegeneration and Regeneration in Alzheimer’s Disease Brain
journal, June 2012
- Varnum, Megan M.; Ikezu, Tsuneya
- Archivum Immunologiae et Therapiae Experimentalis, Vol. 60, Issue 4
Amoeboid Microglia in the Periventricular White Matter Induce Oligodendrocyte Damage through Expression of Proinflammatory Cytokines via MAP Kinase Signaling Pathway in Hypoxic Neonatal Rats
journal, July 2008
- Deng, YiYu; Lu, Jia; Sivakumar, Viswanathan
- Brain Pathology, Vol. 18, Issue 3
Differential cellular responses in healthy mice and in mice with established airway inflammation when exposed to hematite nanoparticles
journal, October 2015
- Gustafsson, Åsa; Bergström, Ulrika; Ågren, Lina
- Toxicology and Applied Pharmacology, Vol. 288, Issue 1
Mechanism-Based Tumor-Targeting Drug Delivery System. Validation of Efficient Vitamin Receptor-Mediated Endocytosis and Drug Release
journal, May 2010
- Chen, Shuyi; Zhao, Xianrui; Chen, Jingyi
- Bioconjugate Chemistry, Vol. 21, Issue 5
A Meta-Analysis of Cytokines in Alzheimer's Disease
journal, November 2010
- Swardfager, Walter; Lanctôt, Krista; Rothenburg, Lana
- Biological Psychiatry, Vol. 68, Issue 10
Differential cytotoxicity exhibited by silica nanowires and nanoparticles
journal, January 2008
- Adili, Abulaiti; Crowe, Saskia; Beaux, Miles F.
- Nanotoxicology, Vol. 2, Issue 1
Siderophore-Mediated Dissolution of Hematite (α-Fe 2 O 3 ): Effects of Nanoparticle Size
journal, May 2012
- Barton, Lauren E.; Quicksall, Andrew N.; Maurice, Patricia A.
- Geomicrobiology Journal, Vol. 29, Issue 4
α-Fe 2 O 3 multi-shelled hollow microspheres for lithium ion battery anodes with superior capacity and charge retention
journal, January 2014
- Xu, Simeng; Hessel, Colin M.; Ren, Hao
- Energy Environ. Sci., Vol. 7, Issue 2
Microglial inhibitory factor (MIF/TKP) mitigates secondary damage following spinal cord injury
journal, September 2012
- Emmetsberger, Jaime; Tsirka, Stella E.
- Neurobiology of Disease, Vol. 47, Issue 3
Tumour necrosis factor converting enzyme (TACE) activity in the colonic mucosa of patients with inflammatory bowel disease
journal, July 2002
- Brynskov, J.; Foegh, P.; Pedersen, G.
- Gut, Vol. 51, Issue 1
Nitric Oxide and Peroxynitrite in Health and Disease
journal, January 2007
- Pacher, Pál; Beckman, Joseph S.; Liaudet, Lucas
- Physiological Reviews, Vol. 87, Issue 1
Carbon nanotubes: toxicological impact on human health and environment
journal, March 2009
- Tejral, Gracian; Panyala, Nagender Reddy; Havel, Josef
- Journal of Applied Biomedicine, Vol. 7, Issue 1
Ambient Large-Scale Template-Mediated Synthesis of High-Aspect Ratio Single-Crystalline, Chemically Doped Rare-Earth Phosphate Nanowires for Bioimaging
journal, December 2009
- Zhang, Fen; Wong, Stanislaus S.
- ACS Nano, Vol. 4, Issue 1
Oligodendrocyte-microglia cross-talk in the central nervous system
journal, February 2014
- Peferoen, Laura; Kipp, Markus; van der Valk, Paul
- Immunology, Vol. 141, Issue 3
Animal Models of MS Reveal Multiple Roles of Microglia in Disease Pathogenesis
journal, January 2011
- Gao, Zhen; Tsirka, Stella E.
- Neurology Research International, Vol. 2011
Microglia: Activation and Their Significance in the Central Nervous System
journal, August 2001
- Nakajima, K.; Kohsaka, S.
- Journal of Biochemistry, Vol. 130, Issue 2
A Meta-Analysis of Cytokines in Major Depression
journal, March 2010
- Dowlati, Yekta; Herrmann, Nathan; Swardfager, Walter
- Biological Psychiatry, Vol. 67, Issue 5
Hematite concave nanocubes and their superior catalytic activity for low temperature CO oxidation
journal, January 2014
- Liang, Hanfeng; Jiang, Xinde; Qi, Zhengbing
- Nanoscale, Vol. 6, Issue 13
Hematite Nanoparticles Larger than 90 nm Show No Sign of Toxicity in Terms of Lactate Dehydrogenase Release, Nitric Oxide Generation, Apoptosis, and Comet Assay in Murine Alveolar Macrophages and Human Lung Epithelial Cells
journal, February 2012
- Freyria, Francesca Stefania; Bonelli, Barbara; Tomatis, Maura
- Chemical Research in Toxicology, Vol. 25, Issue 4
The potential environmental impact of engineered nanomaterials
journal, September 2003
- Colvin, Vicki L.
- Nature Biotechnology, Vol. 21, Issue 10
Silica-coated super-paramagnetic iron oxide nanoparticles (SPIONPs): a new type contrast agent of T 1 magnetic resonance imaging (MRI)
journal, January 2015
- Iqbal, M. Zubair; Ma, Xuehua; Chen, Tianxiang
- Journal of Materials Chemistry B, Vol. 3, Issue 26
M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination
journal, July 2013
- Miron, Veronique E.; Boyd, Amanda; Zhao, Jing-Wei
- Nature Neuroscience, Vol. 16, Issue 9
Lipopolysaccharide-induced microglial activation in culture: temporal profiles of morphological change and release of cytokines and nitric oxide
journal, November 1999
- Nakamura, Y.; Si, Q. S.; Kataoka, K.
- Neuroscience Research, Vol. 35, Issue 2
Shape and size controlled α-Fe2O3 nanoparticles as supports for gold-catalysts: Synthesis and influence of support shape and size on catalytic performance
journal, July 2009
- Wang, Guang-Hui; Li, Wen-Cui; Jia, Kun-Ming
- Applied Catalysis A: General, Vol. 364, Issue 1-2, p. 42-47
Assessing Activation States in Microglia
journal, April 2010
- Colton, Carol A.; Wilcock, Donna M.
- CNS & Neurological Disorders - Drug Targets, Vol. 9, Issue 2
Potential neurological lesion after nasal instillation of TiO2 nanoparticles in the anatase and rutile crystal phases
journal, December 2008
- Wang, J.; Chen, C.; Liu, Y.
- Toxicology Letters, Vol. 183, Issue 1-3
A comparative review of cell culture systems for the study of microglial biology in Alzheimer’s disease
journal, May 2012
- Stansley, Branden; Post, Jan; Hensley, Kenneth
- Journal of Neuroinflammation, Vol. 9, Issue 1
Robust Uptake of Magnetic Nanoparticles (MNPs) by Central Nervous System (CNS) Microglia: Implications for Particle Uptake in Mixed Neural Cell Populations
journal, March 2010
- Pickard, Mark; Chari, Divya
- International Journal of Molecular Sciences, Vol. 11, Issue 3
Synthesis of Cholesterol-Conjugated Magnetic Nanoparticles for Purification of Human Paraoxonase 1
journal, November 2009
- Samra, Zahoor Qadir; Shabir, Sadaf; Rehmat, Zainab
- Applied Biochemistry and Biotechnology, Vol. 162, Issue 3
Goethite hierarchical nanostructures: Glucose-assisted synthesis, chemical conversion into hematite with excellent photocatalytic properties
journal, May 2011
- Tong, Guoxiu; Guan, Jianguo; Zhang, Qingjie
- Materials Chemistry and Physics, Vol. 127, Issue 1-2
Theoretical study of electronic, magnetic, and structural properties of α- (hematite)
journal, March 1995
- Catti, M.; Valerio, G.; Dovesi, R.
- Physical Review B, Vol. 51, Issue 12
Detection of Necrosis by Release of Lactate Dehydrogenase Activity
book, January 2013
- Chan, Francis Ka-Ming; Moriwaki, Kenta; De Rosa, María José
- Immune Homeostasis. Methods in Molecular Biology
Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity
journal, October 2007
- Calabrese, Vittorio; Mancuso, Cesare; Calvani, Menotti
- Nature Reviews Neuroscience, Vol. 8, Issue 10
Facile synthesis of uniform α-Fe2O3 crystals and their facet-dependent catalytic performance in the photo-Fenton reaction
journal, January 2013
- Zhao, Yubao; Pan, Feng; Li, Hui
- Journal of Materials Chemistry A, Vol. 1, Issue 24
Shape and Aggregation Control of Nanoparticles: Not Shaken, Not Stirred
journal, January 2006
- Li, Dan; Kaner, Richard B.
- Journal of the American Chemical Society, Vol. 128, Issue 3
Dual docetaxel/superparamagnetic iron oxide loaded nanoparticles for both targeting magnetic resonance imaging and cancer therapy
journal, October 2011
- Ling, You; Wei, Kun; Luo, Yun
- Biomaterials, Vol. 32, Issue 29
α-Fe 2 O 3 Nanocolumns and Nanorods Fabricated by Electron Beam Evaporation for Visible Light Photocatalytic and Antimicrobial Applications
journal, March 2013
- Basnet, Pradip; Larsen, George K.; Jadeja, Ravirajsinh P.
- ACS Applied Materials & Interfaces, Vol. 5, Issue 6
Identification of Two Distinct Macrophage Subsets with Divergent Effects Causing either Neurotoxicity or Regeneration in the Injured Mouse Spinal Cord
journal, October 2009
- Kigerl, K. A.; Gensel, J. C.; Ankeny, D. P.
- Journal of Neuroscience, Vol. 29, Issue 43
Pinocytosis as a select marker of ramified microglia in vivo and in vitro.
journal, June 1991
- Ranson, P. A.; Thomas, W. E.
- Journal of Histochemistry & Cytochemistry, Vol. 39, Issue 6
Culturing Microglia from the Neonatal and Adult Central Nervous System
journal, January 2013
- Bronstein, Robert; Torres, Luisa; Nissen, Jillian C.
- Journal of Visualized Experiments, Issue 78
Using iron oxide nanoparticles to diagnose CNS inflammatory diseases and PCNSL
journal, June 2013
- Farrell, B. T.; Hamilton, B. E.; Dosa, E.
- Neurology, Vol. 81, Issue 3
The translocation of fullerenic nanoparticles into lysosome via the pathway of clathrin-mediated endocytosis
journal, March 2008
- Li, Wei; Chen, Chunying; Ye, Chang
- Nanotechnology, Vol. 19, Issue 14
Cytotoxicity of Nanoparticles
journal, January 2008
- Lewinski, Nastassja; Colvin, Vicki; Drezek, Rebekah
- Small, Vol. 4, Issue 1
Uniform PEGylated PLGA Microcapsules with Embedded Fe 3 O 4 Nanoparticles for US/MR Dual-Modality Imaging
journal, August 2015
- Xu, Sijia; Yang, Fei; Zhou, Xiao
- ACS Applied Materials & Interfaces, Vol. 7, Issue 36
Selective Nanovector Mediated Treatment of Activated Proinflammatory Microglia/Macrophages in Spinal Cord Injury
journal, October 2013
- Papa, Simonetta; Rossi, Filippo; Ferrari, Raffaele
- ACS Nano, Vol. 7, Issue 11
Water‐Dispersible, Multifunctional, Magnetic, Luminescent Silica‐Encapsulated Composite Nanotubes
journal, January 2010
- Zhou, Hongjun; Chen, Jingyi; Sutter, Eli
- Small, Vol. 6, Issue 3
Targeted drug delivery via the folate receptor
journal, March 2000
- Sudimack, Jennifer; Lee, Robert J.
- Advanced Drug Delivery Reviews, Vol. 41, Issue 2