Encyclopedia of Nanotechnology

Living Edition
| Editors: Bharat Bhushan

Cellular Mechanisms of Nanoparticle Toxicity

  • Francelyne Marano
  • Fernando Rodrigues-Lima
  • Jean-Marie Dupret
  • Armelle Baeza-Squiban
  • Sonja Boland
Living reference work entry
DOI: https://doi.org/10.1007/978-94-007-6178-0_175-2



The interaction between nanoparticles and cell triggers a cascade of molecular events which could induce a toxicity and cell death. They are associated with the uptake of nanoparticles, their persistence at cellular level, and their ability to release free radicals and to induce an oxidative stress. The resulting activation of molecular pathways and transcription factors could lead to a pro-inflammatory response or, depending on the level of free radicals, apoptosis.


The last 5 years have shown an increasing number of papers on the mechanisms of nanoparticle (NP) cytotoxicity. What are the reasons? It is likely that the specific useful properties which appear at nanoscale can also lead to adverse effects. This hypothesis is strongly supported by in vivo and in vitro studies to compare the toxicity of NPs with their fine counterparts of the same chemical composition. These results have clearly demonstrated a...


Reactive Oxygen Species Diesel Exhaust Particle Specific Signaling Pathway Spontaneous Reactive Oxygen Species Lysosomal Membrane Destabilization 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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  1. 1.
    Donaldson, K., Borm, P.: Particle Toxicology, p. 434. CRC Press, Boca Raton, Florida, USA (2007)Google Scholar
  2. 2.
    Oberdorster, G., Oberdorster, E., Oberdorster, J.: Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ. Health Perspect. 113, 823–839 (2005)CrossRefGoogle Scholar
  3. 3.
    Brunekreef, B., Holgate, S.T.: Air pollution and health. Lancet 360, 1233–1242 (2002)CrossRefGoogle Scholar
  4. 4.
    Marano, F., Boland, S., Baeza-Squiban, A.: Particle-associated organics and proinflammatory signaling. In: Donaldson, K., Borm, P. (eds.) Particle Toxicology, pp. 211–226. CRC Press, Boca Raton, Florida, USA (2007)Google Scholar
  5. 5.
    Nel, A., Xia, T., Madler, L., Li, N.: Toxic potential of materials at the nanolevel. Science 311, 622–627 (2006)CrossRefGoogle Scholar
  6. 6.
    Unfried, K., Albrecht, C., Klotz, L.O., Mikecz, A.V., Grether-Beck, S., Schins, R.P.F.: Cellular responses to nanoparticles: target structures and mechanisms. Nanotoxicology 1, 52–71 (2007)CrossRefGoogle Scholar
  7. 7.
    Nel, A.E., Madler, L., Velegol, D., Xia, T., Hoek, E.M., Somasundaran, P., Klaessig, F., Castranova, V., Thompson, M.: Understanding biophysicochemical interactions at the nano-bio interface. Nat. Mater. 8, 543–557 (2009)CrossRefGoogle Scholar
  8. 8.
    Lynch, I., Salvati, A., Dawson, K.A.: Protein-nanoparticle interactions: what does the cell see? Nat. Nanotechnol. 4, 546–547 (2009)CrossRefGoogle Scholar
  9. 9.
    Huang, Y.F., Liu, H., Xiong, X., Chen, Y., Tan, W.: Nanoparticle-mediated IgE-receptor aggregation and signaling in RBL mast cells. J. Am. Chem. Soc. 131, 17328–17334 (2009)CrossRefGoogle Scholar
  10. 10.
    Bhabra, G., Sood, A., Fisher, B., Cartwright, L., Saunders, M., Evans, W.H., Surprenant, A., Lopez-Castejon, G., Mann, S., Davis, S.A., Hails, L.A., Ingham, E., Verkade, P., Lane, J., Heesom, K., Newson, R., Case, C.P.: Nanoparticles can cause DNA damage across a cellular barrier. Nat. Nanotechnol. 4, 876–883 (2009)CrossRefGoogle Scholar
  11. 11.
    Marano, F., Hussain, S., Rodriges-Lima, F., Baeza-Squiban, A., Boland, S.: Nanoparticles: molecular target and cell signaling. Arch. Toxicol. 85(7):733-41 (2011)Google Scholar
  12. 12.
    Dawson, K.A., Salvati, A., Lynch, I.: Nanotoxicology: nanoparticles reconstruct lipids. Nat. Nanotechnol. 4, 84–85 (2009)CrossRefGoogle Scholar
  13. 13.
    Rejman, J., Oberle, V., Zuhorn, I.S., Hoekstra, D.: Size-dependent internalization of particles via the pathways of clathrin- and caveolae-mediated endocytosis. Biochem. J. 377, 159–169 (2004)CrossRefGoogle Scholar
  14. 14.
    Hussain, S., Boland, S., Baeza-Squiban, A., Hamel, R., Thomassen, L.C., Martens, J.A., Billon-Galland, M.A., Fleury-Feith, J., Moisan, F., Pairon, J.C., Marano, F.: Oxidative stress and proinflammatory effects of carbon black and titanium dioxide nanoparticles: role of particle surface area and internalized amount. Toxicology 260, 142–149 (2009)CrossRefGoogle Scholar
  15. 15.
    Gratton, S.E., Ropp, P.A., Pohlhaus, P.D., Luft, J.C., Madden, V.J., Napier, M.E., Desimone, J.M.: The effect of particle design on cellular internalization pathways. Proc. Natl. Acad. Sci. U. S. A. 105, 11613–11618 (2008)CrossRefGoogle Scholar
  16. 16.
    Xia, T., Kovochich, M., Liong, M., Zink, J.I., Nel, A.E.: Cationic polystyrene nanosphere toxicity depends on cell-specific endocytic and mitochondrial injury pathways. ACS Nano 2, 85–96 (2008)CrossRefGoogle Scholar
  17. 17.
    Ayres, J.G., Borm, P., Cassee, F.R., Castranova, V., Donaldson, K., Ghio, A., Harrison, R.M., Hider, R., Kelly, F., Kooter, I.M., Marano, F., Maynard, R.L., Mudway, I., Nel, A., Sioutas, C., Smith, S., Baeza-Squiban, A., Cho, A., Duggan, S., Froines, J.: Evaluating the toxicity of airborne particulate matter and nanoparticles by measuring oxidative stress potential – a workshop report and consensus statement. Inhal. Toxicol. 20, 75–99 (2008)CrossRefGoogle Scholar
  18. 18.
    Sydlik, U., Bierhals, K., Soufi, M., Abel, J., Schins, R.P., Unfried, K.: Ultrafine carbon particles induce apoptosis and proliferation in rat lung epithelial cells via specific signaling pathways both using EGF-R. Am. J. Physiol. Lung Cell. Mol. Physiol. 291, L725–L733 (2006)CrossRefGoogle Scholar
  19. 19.
    Moller, W., Brown, D.M., Kreyling, W.G., Stone, V.: Ultrafine particles cause cytoskeletal dysfunctions in macrophages: role of intracellular calcium. Part. Fibre Toxicol. 2, 7 (2005)CrossRefGoogle Scholar
  20. 20.
    Hussain, S., Thomassen, L.C., Feracatu, I., Borot, M.C., Andreau, K., Fleury, J., Baeza-Squiban, A., Marano, F., Boland, S.: Carbon black and titanium oxide nanoparticles elicit distinct apoptosic pathways in bronchial epithelial cells. Part. Fibre.Toxicol. 7(10), 1–17 (2010). Online 16 AprGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Francelyne Marano
    • 1
  • Fernando Rodrigues-Lima
    • 1
  • Jean-Marie Dupret
    • 1
  • Armelle Baeza-Squiban
    • 1
  • Sonja Boland
    • 1
  1. 1.Unit of Functional and Adaptive Biology (BFA), Laboratory of Molecular and Cellular Responses to Xenobiotics, UMR CNRS 8251Univ Paris Diderot, (Sorbonne Paris Cité)Paris cedex 13France