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Differential toxicity of amorphous silica nanoparticles toward phagocytic and epithelial cells

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Abstract

The objective of this study was to evaluate the influence of size and surface functionality of amorphous silica nanoparticles (SNPs) on their interaction with cultured cells. The intracellular uptake, phagocytic activity, and possible mechanisms of toxicity induced by SNPs were studied on murine alveolar macrophages and two epithelial cancer cell lines. It was found that phagocytic cells are more susceptible to amorphous SNPs than epithelial cells. SNPs with functionalized surfaces were capable to induce the formation of apoptotic cells to a higher extent than plain particles. Plain SNPs induced plasma membrane damage in phagocytic cells to a higher extent and caused cell death in a shorter period of time than surface-functionalized SNPs. The prevalence of necrotic mode of cell death was observed after treatment with plain SNPs. In the range studied surface functionality played an important role in SNPs toxicity.

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References

  • Arnida, Malugin A, Ghandehari H (2010) Cellular uptake and toxicity of gold nanoparticles in prostate cancer cells: a comparative study of rods and spheres. J Appl Toxicol 30:212–217

    CAS  Google Scholar 

  • Barnes CA, Elsaesser A, Arkusz J, Smok A, Palus J, Leśniak A, Salvati A, Hanrahan JP, Jong WH, Dziubałtowska E, Stepnik M, Rydzyński K, McKerr G, Lynch I, Dawson KA, Howard CV (2008) Reproducible comet assay of amorphous silica nanoparticles detects no genotoxicity. Nano Lett 8:3069–3074

    Article  CAS  Google Scholar 

  • Bharali DJ, Klejbor I, Stachowiak EK, Dutta P, Roy I, Kaur N, Bergey EJ, Prasad PN, Stachowiak MK (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  CAS  Google Scholar 

  • Bogunia-Kubik K, Sugisaka M (2002) From molecular biology to nanotechnology and nanomedicine. Biosystems 65:123–138

    Article  CAS  Google Scholar 

  • Borm P, Klaessig FC, Landry TD, Moudgil B, Pauluhn J, Thomas K, Trottier R, Wood S (2006) Research strategies for safety evaluation of nanomaterials, part V: role of dissolution in biological fate and effects of nanoscale particles. Toxicol Sci 90:23–32

    Article  CAS  Google Scholar 

  • Chang JS, Chang KL, Hwang DF, Kong ZL (2007) In vitro cytotoxicity of silica nanoparticles at high concentrations strongly depends on the metabolic activity type of the cell line. Environ Sci Technol 41:2064–2068

    Article  CAS  Google Scholar 

  • Chen M, von Mikecz A (2005) Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO2 nanoparticles. Exp Cell Res 305:51–62

    Article  CAS  Google Scholar 

  • Choi J, Zheng Q, Katz HE, Guilarte TR (2010) Silica-based nanoparticle uptake and cellular response by primary microglia. Environ Health Perspect 118:589–595

    Article  CAS  Google Scholar 

  • Darzynkiewicz Z, Juan G, Bedner E (1999) Determining cell cycle stages by flow cytometry. In: Bonifacino JS, Dasso M, Harford JB, Lippincott-Schwartz J, Yamada KM (eds) Current protocols in cell biology. Wiley, New York, pp 8.4.1–8.4.18

    Google Scholar 

  • De Jong WH, Borm PJ (2008) Drug delivery and nanoparticles: applications and hazards. Int J Nanomed 3:133–149

    Article  Google Scholar 

  • Geiser M, Rothen-Rutishauser B, Kapp N, Schurch S, Kreyling W, Schulz H, Semmler M, Im Hof V, Heyder J, Gehr P (2005) Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells. Environ Health Perspect 113:1555–1560

    Article  Google Scholar 

  • Gemeinhart RA, Luo D, Saltzman WM (2005) Cellular fate of a modular DNA delivery system mediated by silica nanoparticles. Biotechnol Prog 21:532–537

    Article  CAS  Google Scholar 

  • Hardman R (2006) A toxicologic review of quantum dots: toxicity depends on physicochemical and environmental factors. Environ Health Perspect 114:165–172

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Hsiao IL, Huang YJ (2011) Effects of various physicochemical characteristics on the toxicities of ZnO and TiO nanoparticles toward human lung epithelial cells. Sci Total Environ 409:1219–1228

    Article  CAS  Google Scholar 

  • Jiang W, Kim BY, Rutka JT, Chan WC (2008) Nanoparticle mediated cellular response is size-dependent. Nat Nanotechnol 3:145–150

    Article  CAS  Google Scholar 

  • Jin Y, Kannan S, Wu M, Zhao JX (2007) Toxicity of luminescent silica nanoparticles to living cells. Chem Res Toxicol 20:1126–1133

    Article  CAS  Google Scholar 

  • Jones CF, Grainger DW (2009) In vitro assessments of nanomaterial toxicity. Adv Drug Delivery Rev 61:438–456

    Article  CAS  Google Scholar 

  • Kanno S, Furuyama A, Hirano S (2007) A murine scavenger receptor MARCO recognizes polystyrene nanoparticles. Toxicol Sci 97:398–406

    Article  CAS  Google Scholar 

  • Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, Blagosklonny MV, El-Deiry WS, Golstein P, Green DR, Hengartner M, Knight RA, Kumar S, Lipton SA, Malorni W, Nuñez G, Peter ME, Tschopp J, Yuan J, Piacentini M, Zhivotovsky B, Melino G (2009) Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ 16:3–11

    Article  CAS  Google Scholar 

  • Lewinski N, Colvin V, Drezek R (2008) Cytotoxicity of nanoparticles. Small 4:26–49

    Article  CAS  Google Scholar 

  • Lin W, Huang YW, Zhou XD, Ma Y (2006) In vitro toxicity of silica nanoparticles in human lung cancer cells. Toxicol Appl Pharmacol 217:252–259

    Article  CAS  Google Scholar 

  • Lison D, Thomassen LC, Rabolli V, Gonzalez L, Napierska D, Seo JW, Kirsch-Volders M, Hoet P, Kirschhock CE, Martens JA (2008) Nominal and effective dosimetry of silica nanoparticles in cytotoxicity assays. Toxicol Sci 104:155–162

    Article  CAS  Google Scholar 

  • Maksimenko O, Pavlov E, Toushov E, Molin A, Stukalov Y, Prudskova T, Feldman V, Kreuter J, Gelperina S (2008) Radiation sterilization of doxorubicin bound to poly(butyl cyanoacrylate) nanoparticles. Int J Pharm 356:325–332

    Article  CAS  Google Scholar 

  • Marquis BJ, Love SA, Braun KL, Haynes CH (2009) Analytical methods to assess nanoparticle toxicity. Analyst 134:425–439

    Article  CAS  Google Scholar 

  • Moghimi SM, Hunter AC, Murray JC (2001) Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol Rev 53:283–284

    CAS  Google Scholar 

  • Moselhy J, Wu XY, Nicholov R, Kodaria K (2000) In vitro studies of the interaction of poly(NIPAM/MAA) nanoparticles with proteins and cells. J Biomater Sci Polym Ed 11:123–147

    Article  CAS  Google Scholar 

  • Murdock RC, Braydich-Stolle L, Schrand AM, Schlager JJ, Hussain SM (2008) Characterization of nanomaterial dispersion in solution prior to in vitro exposure using dynamic light scattering technique. Toxicol Sci 101:239–253

    Article  CAS  Google Scholar 

  • Napierska D, Thomassen LC, Rabolli V, Lison D, Gonzalez L, Kirsch-Volders M, Martens JA, Hoet PH (2009) Size-dependent cytotoxicity of monodisperse silica nanoparticles in human endothelial cells. Small 5:846–853

    Article  CAS  Google Scholar 

  • Napierska D, Thomassen LC, Lison D, Martens JA, Hoet PH (2010) The nanosilica hazard: another variable entity. Part Fibre Toxicol 7:39

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Oberdörster G, Oberdörster E, Oberdörster J (2005) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113:823–839

    Article  Google Scholar 

  • Porter AE, Muller K, Skepper J, Midgley P, Welland M (2006) Uptake of C60 by human monocyte macrophages, its localization and implications for toxicity: studied by high resolution electron microscopy and electron tomography. Acta Biomater 2:409–419

    Article  Google Scholar 

  • Qhobosheane M, Santra S, Zhang P, Tan W (2001) Biochemically functionalized silica nanoparticles. Analyst 126:1274–1278

    Article  CAS  Google Scholar 

  • Russell-Jones GJ, Arthur L, Walker H (1999) Vitamin B12-mediated transport of nanoparticles across Caco-2 cells. Int J Pharm 179:247–255

    Article  CAS  Google Scholar 

  • Sayes CM, Wahi R, Kurian P, Liu Y, West J, Ausman K, Warheit D, Colvin VL (2006) Correlating nanoscale titania structure with toxicity. Toxicol Sci 92:174–185

    Article  CAS  Google Scholar 

  • Sayes CM, Reed KL, Warheit DB (2007) Assessing toxicity of fine and nanoparticles: comparing in vitro measurements to in vivo pulmonary toxicity profiles. Toxicol Sci 97:163–180

    Article  CAS  Google Scholar 

  • Shvedova AA, Castranova V, Kisin ER, Schwegler-Berry D, Murray AR, Gandelsman VZ, Maynard A, Baron P (2003) Exposure to carbon nanotube material: assessment of nanotube cytotoxicity using human keratinocyte cells. J Toxicol Environ Health 66:1909–1926

    Article  CAS  Google Scholar 

  • Singh R, Lillard JW Jr (2009) Nanoparticle-based targeted drug delivery. Exp Mol Pathol 86:215–223

    Article  CAS  Google Scholar 

  • Steiniger SC, Kreuter J, Khalansky AS, Skidan IN, Bobruskin AI, Smirnova ZS, Severin SE, Uhl R, Kock M, Geiger KD, Gelperina SE (2004) Chemotherapy of glioblastoma in rats using doxorubicin-loaded nanoparticles. Int J Cancer 109:759–767

    Article  CAS  Google Scholar 

  • Teeguarden JG, Hinderliter PM, Orr G, Thrall BD, Pounds JG (2007) Particokinetics in vitro: dosimetry considerations for in vitro nanoparticle toxicity assessments. Toxicol Sci 95:300–312

    Article  CAS  Google Scholar 

  • Tsoli M, Kuhn H, Brandau W, Esche H, Schmid G (2005) Cellular uptake and toxicity of Au55 clusters. Small 1:841–844

    Article  CAS  Google Scholar 

  • Unfried K, Albrecht C, Klotz LO, von Mikecz A, Grether-Beck S, Schins RPF (2007) Cellular responses to nanoparticles: target structures and mechanisms. Nanotoxicology 1:1–20

    Article  Google Scholar 

  • Venkatesan N, Yoshimitsu J, Ito Y, Shibata N, Takada K (2005) Liquid filled nanoparticles as a drug delivery tool for protein therapeutics. Biomaterials 26:7154–7163

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Wottrich R, Diabaté S, Krug HF (2004) Biological effects of ultrafine model particles in human macrophages and epithelial cells in mono- and co-culture. Int J Hyg Environ Health 207:353–361

    Article  CAS  Google Scholar 

  • Xie G, Sun J, Zhong G, Shi L, Zhang D (2009) Biodistribution and toxicity of intravenously administered silica nanoparticles in mice. Arch Toxicol. doi:10.1007/s00204-009-0488-x

  • Yin H, Casey PS, McCall MJ (2010) Surface modifications of ZnO nanoparticles and their cytotoxicity. J Nanosci Nanotechnol 10:7565–7570

    Article  CAS  Google Scholar 

  • Zhang FF, Wan Q, Li CX, Wang XL, Zhu ZQ, Xian YZ, Jin LT, Yamamoto K (2004) Simultaneous assay of glucose, lactate, l-glutamate and hypoxanthine levels in a rat striatum using enzyme electrodes based on neutral red-doped silica nanoparticles. Anal Bioanal Chem 380:637–642

    Article  CAS  Google Scholar 

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Acknowledgments

We thank Dr. Chris Rodesh and Nancy Chandler from the University of Utah Core Facilities for help with CLSM and TEM imaging, respectively. This work was supported by the National Institutes of Health (R01DE19050), the National Science Foundation (NSF-NIRT-ID 0835342), and by the Utah Science Technology and Research (USTAR) Initiative.

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Authors and Affiliations

  1. Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA

    Alexander Malugin & Hamidreza Ghandehari

  2. Department of Bioengineering, University of Utah, Salt Lake City, UT, USA

    Heather Herd & Hamidreza Ghandehari

  3. Utah Center for Nanomedicine, Nano Institute of Utah, University of Utah, Salt Lake City, UT, 84108, USA

    Alexander Malugin, Heather Herd & Hamidreza Ghandehari

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  1. Alexander Malugin
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  2. Heather Herd
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Correspondence to Hamidreza Ghandehari.

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Malugin, A., Herd, H. & Ghandehari, H. Differential toxicity of amorphous silica nanoparticles toward phagocytic and epithelial cells. J Nanopart Res 13, 5381 (2011). https://doi.org/10.1007/s11051-011-0524-7

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  • DOI: https://doi.org/10.1007/s11051-011-0524-7

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