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Suppression of nanosilica particle-induced inflammation by surface modification of the particles

  • Inorganic Compounds
  • Published:
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Abstract

It has gradually become evident that nanomaterials, which are widely used in cosmetics, foods, and medicinal products, could induce substantial inflammation. However, the roles played by the physical characteristics of nanomaterials in inflammatory responses have not been elucidated. Here, we examined how particle size and surface modification influenced the inflammatory effects of nanosilica particles, and we investigated the mechanisms by which the particles induced inflammation. We compared the inflammatory effects of silica particles with diameters of 30–1,000 nm in vitro and in vivo. In macrophages in vitro, 30- and 70-nm nanosilica particles (nSP30 and nSP70) induced higher production of tumor necrosis factor-α (TNFα) than did larger particles. In addition, intraperitoneal injection of nSP30 and nSP70 induced stronger inflammatory responses involving cytokine production than did larger particles in mice. nSP70-induced TNFα production in macrophage depended on the production of reactive oxygen species and the activation of mitogen-activated protein kinases (MAPKs). Furthermore, nSP70-induced inflammatory responses were dramatically suppressed by surface modification of the particles with carboxyl groups in vitro and in vivo; the mechanism of the suppression involved reduction in MAPK activation. These results provide basic information that will be useful for the development of safe nanomaterials.

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Abbreviations

BHA:

Butylated hydroxyanisole

DPI:

Diphenyleneiodonium chloride

ELISA:

Enzyme-linked immunosorbent assay

ERK:

Extracellular signal-regulated kinase

IL:

Interleukin

JNK:

C-jun N-terminal kinase

KC:

Keratinocyte chemoattractant

MAPKs:

Mitogen-activated protein kinases

MCP-1:

Macrophage chemoattractant protein-1

PBS:

Phosphate-buffered saline

PCLF:

Peritoneal cavity lavage fluid

ROS:

Reactive oxygen species

TEM:

Transmission electron microscopy

TNFα:

Tumor necrosis factor-α

References

  • Albrecht C, Schins RP, Hohr D, Becker A, Shi T, Knaapen AM et al (2004) Inflammatory time course after quartz instillation: role of tumor necrosis factor-alpha and particle surface. Am J Respir Cell Mol Biol 31:292–301

    Article  PubMed  CAS  Google Scholar 

  • Bharali DJ, Klejbor I, Stachowiak EK, Dutta P, Roy I, Kaur N et al (2005) Organically modified silica nanoparticles: a nonviral vector for in vivo gene delivery and expression in the brain. Proc Natl Acad Sci USA 102:11539–11544

    Article  PubMed  CAS  Google Scholar 

  • Bottini M, D’Annibale F, Magrini A, Cerignoli F, Arimura Y, Dawson MI et al (2007) Quantum dot-doped silica nanoparticles as probes for targeting of T-lymphocytes. Int J Nanomedicine 2:227–233

    PubMed  CAS  Google Scholar 

  • Bubici C, Papa S, Dean K, Franzoso G (2006) Mutual cross-talk between reactive oxygen species and nuclear factor-kappa B: molecular basis and biological significance. Oncogene 25:6731–6748

    Article  PubMed  CAS  Google Scholar 

  • Busuttil SJ, Ploplis VA, Castellino FJ, Tang L, Eaton JW, Plow EF (2004) A central role for plasminogen in the inflammatory response to biomaterials. J Thromb Haemost 2:1798–1805

    Article  PubMed  CAS  Google Scholar 

  • Chen Z, Meng H, Xing G, Yuan H, Zhao F, Liu R et al (2008) Age-related differences in pulmonary and cardiovascular responses to SiO2 nanoparticle inhalation: nanotoxicity has susceptible population. Environ Sci Technol 42:8985–8992

    Article  PubMed  CAS  Google Scholar 

  • Decuzzi P, Godin B, Tanaka T, Lee SY, Chiappini C, Liu X et al (2010) Size and shape effects in the biodistribution of intravascularly injected particles. J Control Release 141:320–327

    Article  PubMed  CAS  Google Scholar 

  • Dostert C, Petrilli V, Van Bruggen R, Steele C, Mossman BT, Tschopp J (2008) Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science 320:674–677

    Article  PubMed  CAS  Google Scholar 

  • He X, Nie H, Wang K, Tan W, Wu X, Zhang P (2008) In vivo study of biodistribution and urinary excretion of surface-modified silica nanoparticles. Anal Chem 80:9597–9603

    Article  PubMed  CAS  Google Scholar 

  • Hirano S, Kanno S, Furuyama A (2008) Multi-walled carbon nanotubes injure the plasma membrane of macrophages. Toxicol Appl Pharmacol 232:244–251

    Article  PubMed  CAS  Google Scholar 

  • Hirsch LR, Stafford RJ, Bankson JA, Sershen SR, Rivera B, Price RE et al (2003) Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance. Proc Natl Acad Sci USA 100:13549–13554

    Article  PubMed  CAS  Google Scholar 

  • Hornung V, Bauernfeind F, Halle A, Samstad EO, Kono H, Rock KL et al (2008) Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol 9:847–856

    Article  PubMed  CAS  Google Scholar 

  • Huaux F (2007) New developments in the understanding of immunology in silicosis. Curr Opin Allergy Clin Immunol 7:168–173

    Article  PubMed  Google Scholar 

  • Iyer R, Hamilton RF, Li L, Holian A (1996) Silica-induced apoptosis mediated via scavenger receptor in human alveolar macrophages. Toxicol Appl Pharmacol 141:84–92

    PubMed  CAS  Google Scholar 

  • Jeffrey KL, Camps M, Rommel C, Mackay CR (2007) Targeting dual-specificity phosphatases: manipulating MAP kinase signalling and immune responses. Nat Rev Drug Discov 6:391–403

    Article  PubMed  CAS  Google Scholar 

  • Kagan VE, Bayir H, Shvedova AA (2005) Nanomedicine and nanotoxicology: two sides of the same coin. Nanomedicine 1:313–316

    Article  PubMed  CAS  Google Scholar 

  • Ke Q, Li J, Ding J, Ding M, Wang L, Liu B et al (2006) Essential role of ROS-mediated NFAT activation in TNF-alpha induction by crystalline silica exposure. Am J Physiol Lung Cell Mol Physiol 291:L257–L264

    Article  PubMed  CAS  Google Scholar 

  • Kops SK, Ratzlaff RE, Meade R, Iverson GM, Askenase PW (1986) Interaction of antigen-specific T cell factors with unique “receptors” on the surface of mast cells: demonstration in vitro by an indirect rosetting technique. J Immunol 136:4515–4524

    PubMed  CAS  Google Scholar 

  • Lesniak A, Campbell A, Monopoli MP, Lynch I, Salvati A, Dawson KA (2010) Serum heat inactivation affects protein corona composition and nanoparticle uptake. Biomaterials 31:9511–9518

    Article  PubMed  CAS  Google Scholar 

  • Li X, Hu Y, Jin Z, Jiang H, Wen J (2009) Silica-induced TNF-alpha and TGF-beta1 expression in RAW264.7 cells are dependent on Src-ERK/AP-1 pathways. Toxicol Mech Methods 19:51–58

    Article  PubMed  CAS  Google Scholar 

  • Limmon GV, Arredouani M, McCann KL, Corn Minor RA, Kobzik L, Imani F (2008) Scavenger receptor class-A is a novel cell surface receptor for double-stranded RNA. Faseb J 22:159–167

    Article  PubMed  CAS  Google Scholar 

  • Liu X, Sun J (2010) Endothelial cells dysfunction induced by silica nanoparticles through oxidative stress via JNK/P53 and NF-kappaB pathways. Biomaterials 31:8198–8209

    Article  PubMed  CAS  Google Scholar 

  • Lundqvist M, Stigler J, Elia G, Lynch I, Cedervall T, Dawson KA (2008) Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts. Proc Natl Acad Sci USA 105:14265–14270

    Article  PubMed  CAS  Google Scholar 

  • Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454:436–444

    Article  PubMed  CAS  Google Scholar 

  • Mitchell LA, Lauer FT, Burchiel SW, McDonald JD (2009) Mechanisms for how inhaled multiwalled carbon nanotubes suppress systemic immune function in mice. Nat Nanotechnol 4:451–456

    Article  PubMed  CAS  Google Scholar 

  • Morel F, Doussiere J, Vignais PV (1991) The superoxide-generating oxidase of phagocytic cells. Physiological, molecular and pathological aspects. Eur J Biochem 201:523–546

    Article  PubMed  CAS  Google Scholar 

  • Morishige T, Yoshioka Y, Inakura H, Tanabe A, Yao X, Narimatsu S et al (2010a) The effect of surface modification of amorphous silica particles on NLRP3 inflammasome mediated IL-1beta production, ROS production and endosomal rupture. Biomaterials 31:6833–6842

    Article  PubMed  CAS  Google Scholar 

  • Morishige T, Yoshioka Y, Tanabe A, Yao X, Tsunoda S, Tsutsumi Y et al (2010b) Titanium dioxide induces different levels of IL-1beta production dependent on its particle characteristics through caspase-1 activation mediated by reactive oxygen species and cathepsin B. Biochem Biophys Res Commun 392:160–165

    Article  PubMed  CAS  Google Scholar 

  • Mossman BT, Churg A (1998) Mechanisms in the pathogenesis of asbestosis and silicosis. Am J Respir Crit Care Med 157:1666–1680

    PubMed  CAS  Google Scholar 

  • Nel A, Xia T, Madler L, Li N (2006) Toxic potential of materials at the nanolevel. Science 311:622–627

    Article  PubMed  CAS  Google Scholar 

  • Poland CA, Duffin R, Kinloch I, Maynard A, Wallace WA, Seaton A et al (2008) Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. Nat Nanotechnol 3:423–428

    Article  PubMed  CAS  Google Scholar 

  • Roy I, Ohulchanskyy TY, Bharali DJ, Pudavar HE, Mistretta RA, Kaur N et al (2005) Optical tracking of organically modified silica nanoparticles as DNA carriers: a nonviral, nanomedicine approach for gene delivery. Proc Natl Acad Sci USA 102:279–284

    Article  PubMed  CAS  Google Scholar 

  • Sager TM, Kommineni C, Castranova V (2008) Pulmonary response to intratracheal instillation of ultrafine versus fine titanium dioxide: role of particle surface area. Part Fibre Toxicol 5:17

    Article  PubMed  Google Scholar 

  • Savici D, He B, Geist LJ, Monick MM, Hunninghake GW (1994) Silica increases tumor necrosis factor (TNF) production, in part, by upregulating the TNF promoter. Exp Lung Res 20:613–625

    Article  PubMed  CAS  Google Scholar 

  • Shiryaev A, Moens U (2010) Mitogen-activated protein kinase p38 and MK2, MK3 and MK5: menage a trois or menage a quatre? Cell Signal 22:1185–1192

    Article  PubMed  CAS  Google Scholar 

  • Takagi A, Hirose A, Nishimura T, Fukumori N, Ogata A, Ohashi N et al (2008) Induction of mesothelioma in p53± mouse by intraperitoneal application of multi-wall carbon nanotube. J Toxicol Sci 33:105–116

    Article  PubMed  CAS  Google Scholar 

  • Thakur SA, Hamilton R Jr, Pikkarainen T, Holian A (2009) Differential binding of inorganic particles to MARCO. Toxicol Sci 107:238–246

    Article  PubMed  CAS  Google Scholar 

  • Thannickal VJ, Fanburg BL (2000) Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol 279:L1005–L1028

    PubMed  CAS  Google Scholar 

  • Verraedt E, Pendela M, Adams E, Hoogmartens J, Martens JA (2009) Controlled release of chlorhexidine from amorphous microporous silica. J Control Release 142:47–52

    Article  PubMed  Google Scholar 

  • Waters KM, Masiello LM, Zangar RC, Tarasevich BJ, Karin NJ, Quesenberry RD et al (2009) Macrophage responses to silica nanoparticles are highly conserved across particle sizes. Toxicol Sci 107:553–569

    Article  PubMed  CAS  Google Scholar 

  • Yamashita K, Yoshioka Y, Higashisaka K, Morishita Y, Yoshida T, Fujimura M et al (2010) Carbon nanotubes elicit DNA damage and inflammatory response relative to their size and shape. Inflammation 33:276–280

    Article  PubMed  CAS  Google Scholar 

  • Yamashita K, Yoshioka Y, Higashisaka K, Mimura K, Morishita Y, Nozaki M et al (2011) Silica and titanium dioxide nanoparticles cause pregnancy complications in mice. Nat Nanotechnol 6:321–328

    Article  PubMed  CAS  Google Scholar 

  • Yang X, Liu J, He H, Zhou L, Gong C, Wang X et al (2010) SiO2 nanoparticles induce cytotoxicity and protein expression alteration in HaCaT cells. Part Fibre Toxicol 7:1

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Ministry of Health, Labor, and Welfare in Japan; the Ministry of Education, Culture, Sports, Science, and Technology of Japan; and the Global COE Program “in silico medicine” at Osaka University.

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Laboratory of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Tomohiro Morishige, Hiroshi Inakura, Aya Tanabe, Shogo Narimatsu, Xinglei Yao, Yohei Mukai, Naoki Okada & Shinsaku Nakagawa

  2. The Center for Advanced Medical Engineering and Informatics, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Yasuo Yoshioka, Shin-ichi Tsunoda, Yasuo Tsutsumi & Shinsaku Nakagawa

  3. Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, Osaka, 567-0085, Japan

    Yasuo Yoshioka, Shin-ichi Tsunoda & Yasuo Tsutsumi

  4. Institute of Pharmaceutics, Zhejiang University, 388 Yuhangtang Road, Hangzhou, 310058, China

    Xinglei Yao

  5. Laboratory of Common Apparatus, Division of Biomedical Research, National Institute of Biomedical Innovation, Osaka, 567-0085, Japan

    Youko Monobe & Takayoshi Imazawa

  6. Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan

    Yasuo Tsutsumi

Authors
  1. Tomohiro Morishige
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  2. Yasuo Yoshioka
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  3. Hiroshi Inakura
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  7. Youko Monobe
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  8. Takayoshi Imazawa
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  9. Shin-ichi Tsunoda
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  10. Yasuo Tsutsumi
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  11. Yohei Mukai
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  12. Naoki Okada
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  13. Shinsaku Nakagawa
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Corresponding authors

Correspondence to Yasuo Yoshioka or Shinsaku Nakagawa.

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Morishige, T., Yoshioka, Y., Inakura, H. et al. Suppression of nanosilica particle-induced inflammation by surface modification of the particles. Arch Toxicol 86, 1297–1307 (2012). https://doi.org/10.1007/s00204-012-0823-5

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  • DOI: https://doi.org/10.1007/s00204-012-0823-5

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