Nanoparticle-Cell Interactions: Overview of Uptake, Intracellular Fate and Induction of Cell Responses

  • Barbara Rothen-RutishauserEmail author
  • Joël Bourquin
  • Alke Petri-Fink
Part of the NanoScience and Technology book series (NANO)


The range of engineered nanoparticles (NPs) designed as specific carriers for biomedical applications, e.g. cell targeting and drug delivery, is still on the raise and the question on how NPs are interacting with single cells and sub-cellular structures remains important. The delivery to the cell surface as well as the interaction of NPs with cellular structures with possible subsequent response is highly influenced by various parameters such as (a) the physico-chemical properties of the NPs, (b) the cell and tissue type and (c) the intracellular fate of the NPs in the various organelles including biopersistence, exocytosis and/or transfer to other cells. The aim of this book chapter is to discuss, on the basis of existing literature, the interaction of NPs with single cells including the intracellular fate and their interference with signaling pathways.



We would like to acknowledge the Swiss National Science Foundation (310030_159847/1), the National Center of Competence in Research for Bio-Inspired Materials and the Adolphe Merkle Foundation for financial support. We kindly thank Dr. Miguel Spuch Calvar for the graphical design.


  1. 1.
    Gwinn, M.R., Vallyathan, V.: Nanoparticles: health effects—pros and cons. Env. Health Perspect. 114, 1818–1825 (2006)CrossRefGoogle Scholar
  2. 2.
    Maynard, A.D., Aitken, R.J., Butz, T., Colvin, V., Donaldson, K., Oberdorster, G., et al.: Safe handling of nanotechnology. Nature 444, 267–269 (2006)CrossRefADSGoogle Scholar
  3. 3.
    ISO/TS 27687 (2008)Google Scholar
  4. 4.
    Alex, S., Tiwari, A.: Functionalized gold nanoparticles: synthesis, properties and applications—a review. J. Nanosci. Nanotechnol. 15, 1869–1894 (2015)CrossRefGoogle Scholar
  5. 5.
    Pelaz, B., Alexiou, C., Alvarez-Puebla, R.A., Alves, F., Andrews, A.M., Ashraf, S., et al.: Diverse applications of nanomedicine. ACS Nano 11, 2313–2381 (2017)CrossRefGoogle Scholar
  6. 6.
    Dahoumane, S.A., Jeffryes, C., Mechouet, M., Agathos, S.N.: Biosynthesis of inorganic nanoparticles: a fresh look at the control of shape, size and composition. Bioengineering (Basel) 4 (2017)Google Scholar
  7. 7.
    Drasler, B., Sayre, P., Steinhäuser, K.G., Petri-Fink, A., Rothen-Rutishauser, B.: In vitro approaches to assess the hazard of nanomaterials. NanoImpact 8, 99–116 (2017)Google Scholar
  8. 8.
    Vietti, G., Lison, D., van den Brule, S.: Mechanisms of lung fibrosis induced by carbon nanotubes: towards an Adverse Outcome Pathway (AOP). Part. Fibre Toxicol. 13, 11 (2016)CrossRefGoogle Scholar
  9. 9.
    Bourquin, J., Milosevic, A., Hauser, D., Lehner, R., Blank, F., Petri-Fink, A., et al.: Biodistribution, clearance, and long-term fate of clinically relevant nanomaterials. Adv. Mater. (2018)Google Scholar
  10. 10.
    Urban, D.A., Rodriguez-Lorenzo, L., Balog, S., Kinnear, C., Rothen-Rutishauser, B., Petri-Fink, A.: Plasmonic nanoparticles and their characterization in physiological fluids. Colloids Surf. B Biointerfaces 137, 39–49 (2016)CrossRefGoogle Scholar
  11. 11.
    Moore, T.L., Rodriguez-Lorenzo, L., Hirsch, V., Balog, S., Urban, D., Jud, C., et al.: Nanoparticle colloidal stability in cell culture media and impact on cellular interactions. Chem. Soc. Rev. 44, 6287–6305 (2015)CrossRefGoogle Scholar
  12. 12.
    Lynch, I., Cedervall, T., Lundqvist, M., Cabaleiro-Lago, C., Linse, S., Dawson, K.A.: The nanoparticle-protein complex as a biological entity; a complex fluids and surface science challenge for the 21st century. Adv. Colloid Interface Sci. 134–135, 167–174 (2007)CrossRefGoogle Scholar
  13. 13.
    Bertoli, F., Garry, D., Monopoli, M.P., Salvati, A., Dawson, K.A.: The intracellular destiny of the protein corona: a study on its cellular internalization and evolution. ACS Nano 10, 10471–10479 (2016)CrossRefGoogle Scholar
  14. 14.
    Mahon, E., Salvati, A., Baldelli, B.F., Lynch, I., Dawson, K.A.: Designing the nanoparticle-biomolecule interface for “targeting and therapeutic delivery”. J. Control. Release 161, 164–174 (2012)CrossRefGoogle Scholar
  15. 15.
    Schottler, S., Landfester, K., Mailander, V.: Controlling the stealth effect of nanocarriers through understanding the protein corona. Angew. Chem. Int. Ed. Engl. 55, 8806–8815 (2016)CrossRefGoogle Scholar
  16. 16.
    Docter, D., Westmeier, D., Markiewicz, M., Stolte, S., Knauer, S.K., Stauber, R.H.: The nanoparticle biomolecule corona: lessons learned - challenge accepted? Chem. Soc. Rev. 44, 6094–6121 (2015)CrossRefGoogle Scholar
  17. 17.
    Frohlich, E.: The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int. J. Nanomedicine 7, 5577–5591 (2012)CrossRefGoogle Scholar
  18. 18.
    Muhlfeld, C., Rothen-Rutishauser, B., Blank, F., Vanhecke, D., Ochs, M., Gehr, P.: Interactions of nanoparticles with pulmonary structures and cellular responses. Am. J. Physiol. Lung Cell. Mol. Physiol. 294, L817–L829 (2008)CrossRefGoogle Scholar
  19. 19.
    Unfried, K., Albrecht, C., Klotz, L.O., von Mikecz, A., Grether-Beck, S., Schins, R.P.: Cellular responses to nanoparticles: target structures and mechanisms. Nanotoxicology 1, 1–20 (2007)CrossRefGoogle Scholar
  20. 20.
    Trimble, W.S., Grinstein, S.: Barriers to the free diffusion of proteins and lipids in the plasma membrane. J. Cell. Biol. 208, 259–271 (2015)CrossRefGoogle Scholar
  21. 21.
    Alberts, B., Bray, D., Johnson, A, Lewis, J., Raff, M., Roberts, K., et al.: Essential Cell Biology: An Introduction to the Molecular Biology of the Cell. Garland Publishing, Inc (1998)Google Scholar
  22. 22.
    Warren, G., Wickner, W.: Organelle inheritance. Cell 84, 395–400 (1996)CrossRefGoogle Scholar
  23. 23.
    Singer, S.J., Nicolson, G.L.: The fluid mosaic model of the structure of cell membranes. Science (New York, N Y) 175, 720–731 (1972)CrossRefADSGoogle Scholar
  24. 24.
    Ritchie, K., Spector, J.: Single molecule studies of molecular diffusion in cellular membranes: determining membrane structure. Biopolymers 87, 95–101 (2007)CrossRefGoogle Scholar
  25. 25.
    Sonnino, S., Prinetti, A.: Membrane domains and the “lipid raft” concept. Curr. Med. Chem. 20, 4–21 (2013)Google Scholar
  26. 26.
    Simons, K., Ikonen, E.: Functional rafts in cell membranes. Nature 387, 569–572 (1997)CrossRefADSGoogle Scholar
  27. 27.
    Hillaireau, H., Couvreur, P.: Nanocarriers’ entry into the cell: relevance to drug delivery. Cell. Mol. Life Sci. 66, 2873–2896 (2009)CrossRefGoogle Scholar
  28. 28.
    Conner, S.D., Schmid, S.L.: Regulated portals of entry into the cell. Nature 422, 37–44 (2003)CrossRefADSGoogle Scholar
  29. 29.
    Fytianos, K., Blank, F., Müller, L.: Cellular uptake mechanisms and detection of nanoparticle uptake by advanced imaging methods. In: Zellner, R., Gehr, P. (eds.) Biological Responses to Nanoscale Particles. Springer (2018)Google Scholar
  30. 30.
    Drasler, B., Vanhecke, D., Rodriguez-Lorenzo, L., Petri-Fink, A., Rothen-Rutishauser, B.: Quantifying nanoparticle cellular uptake: which method is best? Nanomedicine (Lond) 12, 1095–1099 (2017)CrossRefGoogle Scholar
  31. 31.
    Elsaesser, A., Taylor, A., de Yanes, G.S., McKerr, G., Kim, E.M., O’Hare, E., et al.: Quantification of nanoparticle uptake by cells using microscopical and analytical techniques. Nanomedicine (Lond) 5, 1447–1457 (2010)CrossRefGoogle Scholar
  32. 32.
    Feliu, N., Huhn, J., Zyuzin, M.V., Ashraf, S., Valdeperez, D., Masood, A., et al.: Quantitative uptake of colloidal particles by cell cultures. Sci. Total Environ. 568, 819–828 (2016)CrossRefADSGoogle Scholar
  33. 33.
    Gottstein, C., Wu, G., Wong, B.J., Zasadzinski, J.A.: Precise quantification of nanoparticle internalization. ACS Nano 7, 4933–4945 (2013)CrossRefGoogle Scholar
  34. 34.
    Vanhecke, D., Rodriguez-Lorenzo, L., Clift, M.J.D., Blank, F., Petri-Fink, A., Rothen-Rutishauser, B.: Quantification of nanoparticles at the single cell level—an overview about state-of-the art techniques and their limitations. Nanomedicine (London, England) 9, 1885–1900 (2014)CrossRefGoogle Scholar
  35. 35.
    Oh, N., Park, J.H.: Endocytosis and exocytosis of nanoparticles in mammalian cells. Int. J. Nanomedicine 9(Suppl 1), 51–63 (2014)Google Scholar
  36. 36.
    Mahmoudi, M., Saeedi-Eslami, S.N., Shokrgozar, M.A., Azadmanesh, K., Hassanlou, M., Kalhor, H.R., et al.: Cell “vision”: complementary factor of protein corona in nanotoxicology. Nanoscale (2012)Google Scholar
  37. 37.
    Kuhn, D.A., Vanhecke, D., Michen, B., Blank, F., Gehr, P., Petri-Fink, A., et al.: Different endocytotic uptake mechanisms for nanoparticles in epithelial cells and macrophages. Beilstein J. Nanotechnol. 5, 1625–1636 (2014)CrossRefGoogle Scholar
  38. 38.
    Doherty, G.J., McMahon, H.T.: Mediation, modulation, and consequences of membrane-cytoskeleton interactions. Annu. Rev. Biophys. 37, 65–95 (2008)CrossRefGoogle Scholar
  39. 39.
    Aderem, A., Underhill, D.M.: Mechanisms of phagocytosis in macrophages. Annu. Rev. Immunol. 17, 593–623 (1999)CrossRefGoogle Scholar
  40. 40.
    Huotari, J., Helenius, A.: Endosome maturation. EMBO J. 30, 3481–3500 (2011)CrossRefGoogle Scholar
  41. 41.
    Anderson, R.G.: The caveolae membrane system. Annu. Rev. Biochem. 67, 199–225 (1998)CrossRefGoogle Scholar
  42. 42.
    Edidin, M.: Membrane cholesterol, protein phosphorylation, and lipid rafts. Sci. STKE 2001, E1 (2001)Google Scholar
  43. 43.
    Brodsky, F.M., Chen, C.Y., Knuehl, C., Towler, M.C., Wakeham, D.E.: Biological basket weaving: formation and function of clathrin-coated vesicles. Annu. Rev. Cell. Dev. Biol. 17, 517–568 (2001)CrossRefGoogle Scholar
  44. 44.
    Schmid, S.L.: Clathrin-coated vesicle formation and protein sorting: an integrated process. Annu. Rev. Biochem. 66, 511–548 (1997)CrossRefGoogle Scholar
  45. 45.
    Geiser, M., Rothen-Rutishauser, B., Kapp, N., Schurch, S., Kreyling, W., Schulz, H., et al.: Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells. Environ. Health Perspect. 113, 1555–1560 (2005)CrossRefGoogle Scholar
  46. 46.
    Lesniak, W., Bielinska, A.U., Sun, K., Janczak, K.W., Shi, X., Baker Jr., J.R., et al.: Silver/dendrimer nanocomposites as biomarkers: fabrication, characterization, in vitro toxicity, and intracellular detection. Nano Lett. 5, 2123–2130 (2005)CrossRefADSGoogle Scholar
  47. 47.
    Mu, Q., Hondow, N.S., Ski, L., Brown, A.P., Jeuken, L.J., Routledge, M.N.: Mechanism of cellular uptake of genotoxic silica nanoparticles. Part. Fibre Toxicol. 9, 29 (2012)CrossRefGoogle Scholar
  48. 48.
    Chu, Z., Zhang, S., Zhang, B., Zhang, C., Fang, C.Y., Rehor, I., et al.: Unambiguous observation of shape effects on cellular fate of nanoparticles. Sci. Rep. 4, 4495 (2014)CrossRefGoogle Scholar
  49. 49.
    Rimai, D.S., Quesnel, D.J., Busnaia, A.A.: The adhesion of dry particles in the nanometer to micrometer size range. Colloids Surf. A Physicochem. Eng. Asp. 165, 3–10 (2000)CrossRefGoogle Scholar
  50. 50.
    Benjaminsen, R.V., Mattebjerg, M.A., Henriksen, J.R., Moghimi, S.M., Andresen, T.L.: The possible “proton sponge” effect of polyethylenimine (PEI) does not include change in lysosomal pH. Mol. Ther. 21, 149–157 (2013)CrossRefGoogle Scholar
  51. 51.
    Brandenberger, C., Muhlfeld, C., Ali, Z., Lenz, A.G., Schmid, O., Parak, W.J., et al.: Quantitative evaluation of cellular uptake and trafficking of plain and polyethylene glycol-coated gold nanoparticles. Small 6, 1669–1678 (2010)CrossRefGoogle Scholar
  52. 52.
    Gray, M., Botelho, R.J.: Phagocytosis: hungry, hungry cells. Methods Mol. Biol. 1519, 1–16 (2017)CrossRefGoogle Scholar
  53. 53.
    Utembe, W., Potgieter, K., Stefaniak, A.B., Gulumian, M.: Dissolution and biodurability: important parameters needed for risk assessment of nanomaterials. Part. Fibre Toxicol. 12, 11 (2015)CrossRefGoogle Scholar
  54. 54.
    Thiele, L., Rothen-Rutishauser, B., Jilek, S., Wunderli-Allenspach, H., Merkle, H.P., Walter, E.: Evaluation of particle uptake in human blood monocyte-derived cells in vitro. does phagocytosis activity of dendritic cells measure up with macrophages? J. Control. Release 76, 59–71 (2001)Google Scholar
  55. 55.
    Thiele, L., Diederichs, J.E., Reszka, R., Merkle, H.P., Walter, E.: Competitive adsorption of serum proteins at microparticles affects phagocytosis by dendritic cells. Biomaterials 24, 1409–1418 (2003)CrossRefGoogle Scholar
  56. 56.
    Bonifacino, J.S., Rojas, R.: Retrograde transport from endosomes to the trans-Golgi network. Nat. Rev. Mol. Cell. Biol. 7, 568–579 (2006)CrossRefGoogle Scholar
  57. 57.
    Wang, C., Zhao, T., Li, Y., Huang, G., White, M.A., Gao, J.: Investigation of endosome and lysosome biology by ultra pH-sensitive nanoprobes. Adv. Drug Deliv. Rev. 113, 87–96 (2017)CrossRefGoogle Scholar
  58. 58.
    Muller, S., Dennemarker, J., Reinheckel, T.: Specific functions of lysosomal proteases in endocytic and autophagic pathways. Biochim. Biophys. Acta 1824, 34–43 (2012)CrossRefGoogle Scholar
  59. 59.
    Kreyling, W.G., Abdelmonem, A.M., Ali, Z., Alves, F., Geiser, M., Haberl, N., et al.: In vivo integrity of polymer-coated gold nanoparticles. Nat. Nanotechnol. 10, 619–623 (2015)CrossRefADSGoogle Scholar
  60. 60.
    Milosevic, A.M., Rodriguez-Lorenzo, L., Balog, S., Monnier, C.A., Petri-Fink, A., Rothen-Rutishauser, B.: Assessing the stability of fluorescently encoded nanoparticles in lysosomes by using complementary methods. Angew. Chem. Int. Ed. Engl. 56, 13382–13386 (2017)CrossRefGoogle Scholar
  61. 61.
    Ma, Z., Bai, J., Jiang, X.: Monitoring of the enzymatic degradation of protein corona and evaluating the accompanying cytotoxicity of nanoparticles. ACS Appl. Mater. Interfaces. 7, 17614–17622 (2015)CrossRefGoogle Scholar
  62. 62.
    Frohlich, E.: Cellular targets and mechanisms in the cytotoxic action of non-biodegradable engineered nanoparticles. Curr. Drug Metab. 14, 976–988 (2013)CrossRefGoogle Scholar
  63. 63.
    Kagan, V.E., Konduru, N.V., Feng, W., Allen, B.L., Conroy, J., Volkov, Y., et al.: Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation. Nat. Nanotechnol. 5, 354–359 (2010)CrossRefADSGoogle Scholar
  64. 64.
    Ma, X., Gong, N., Zhong, L., Sun, J., Liang, X.J.: Future of nanotherapeutics: targeting the cellular sub-organelles. Biomaterials 97, 10–21 (2016)CrossRefGoogle Scholar
  65. 65.
    Lu, P., Bruno, B.J., Rabenau, M., Lim, C.S.: Delivery of drugs and macromolecules to the mitochondria for cancer therapy. J. Control. Release 240, 38–51 (2016)CrossRefGoogle Scholar
  66. 66.
    Wongrakpanich, A., Geary, S.M., Joiner, M.L., Anderson, M.E., Salem, A.K.: Mitochondria-targeting particles. Nanomedicine (Lond) 9, 2531–2543 (2014)CrossRefGoogle Scholar
  67. 67.
    Tammam, S.N., Azzazy, H.M., Lamprecht, A.: How successful is nuclear targeting by nanocarriers? J. Control. Release 229, 140–153 (2016)CrossRefGoogle Scholar
  68. 68.
    Larsen, J., Ross, N., Sullivan, M.: Requirements for the nuclear entry of polyplexes and nanoparticles during mitosis. J. Gene Med. 14, 580–589 (2011)CrossRefGoogle Scholar
  69. 69.
    Burgess, T.L., Kelly, R.B.: Constitutive and regulated secretion of proteins. Annu. Rev. Cell. Biol. 3, 243–293 (1987)CrossRefGoogle Scholar
  70. 70.
    Dombu, C.Y., Kroubi, M., Zibouche, R., Matran, R., Betbeder, D.: Characterization of endocytosis and exocytosis of cationic nanoparticles in airway epithelium cells. Nanotechnology 21, 355102 (2010)CrossRefGoogle Scholar
  71. 71.
    Chithrani, B.D., Ghazani, A.A., Chan, W.C.: Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett. 6, 662–668 (2006)CrossRefADSGoogle Scholar
  72. 72.
    Chu, Z., Huang, Y., Tao, Q., Li, Q.: Cellular uptake, evolution, and excretion of silica nanoparticles in human cells. Nanoscale 3, 3291–3299 (2011)CrossRefADSGoogle Scholar
  73. 73.
    Sakhtianchi, R., Minchin, R.F., Lee, K.B., Alkilany, A.M., Serpooshan, V., Mahmoudi, M.: Exocytosis of nanoparticles from cells: role in cellular retention and toxicity. Adv. Colloid Interface Sci. 201–202, 18–29 (2013)CrossRefGoogle Scholar
  74. 74.
    Symens, N., Soenen, S.J., Rejman, J., Braeckmans, K., De Smedt, S.C., Remaut, K.: Intracellular partitioning of cell organelles and extraneous nanoparticles during mitosis. Adv. Drug Deliv. Rev. 64, 78–94 (2012)CrossRefGoogle Scholar
  75. 75.
    Iversen, T.G., Skotland, T., Sandvig, K.: Endocytosis and intracellular transport of nanoparticles: present knowledge and need for future studies. Nano Today 6, 176–185 (2011)CrossRefGoogle Scholar
  76. 76.
    Lujan, H., Sayes, C.: Cytotoxicological pathways induced after nanoparticle exposure: studies of oxidative stress at the ‘nano-bio’ interface. Toxicol. Res. 6, 580 (2017)CrossRefGoogle Scholar
  77. 77.
    Gonzalez-Flecha, B.: Oxidant mechanisms in response to ambient air particles. Mol. Asp. Med. 25, 169–182 (2004)CrossRefGoogle Scholar
  78. 78.
    Muller, J., Huaux, F., Moreau, N., Misson, P., Heilier, J.F., Delos, M., et al.: Respiratory toxicity of multi-wall carbon nanotubes. Toxicol. Appl. Pharmacol. 207, 221–231 (2005)CrossRefGoogle Scholar
  79. 79.
    Vinzents, P.S., Moller, P., Sorensen, M., Knudsen, L.E., Hertel, O., Jensen, F.P., et al.: Personal exposure to ultrafine particles and oxidative DNA damage. Environ. Health Perspect. 113, 1485–1490 (2005)CrossRefGoogle Scholar
  80. 80.
    Clift, M.J., Gehr, P., Rothen-Rutishauser, B.: Nanotoxicology: a perspective and discussion of whether or not in vitro testing is a valid alternative. Arch. Toxicol. 85, 723–731 (2011)CrossRefGoogle Scholar
  81. 81.
    Kroll, A., Pillukat, M.H., Hahn, D., Schnekenburger, J.: Interference of engineered nanoparticles with in vitro toxicity assays. Arch. Toxicol. 86, 1123–1136 (2012)CrossRefGoogle Scholar
  82. 82.
    Donaldson, K., Stone, V., Borm, P.J., Jimenez, L.A., Gilmour, P.S., Schins, R.P., et al.: Oxidative stress and calcium signaling in the adverse effects of environmental particles (PM10). Free Radic. Biol. Med. 34, 1369–1382 (2003)CrossRefGoogle Scholar
  83. 83.
    Kroll, A., Gietl, J.K., Wiesmuller, G.A., Gunsel, A., Wohlleben, W., Schnekenburger, J., et al.: In vitro toxicology of ambient particulate matter: correlation of cellular effects with particle size and components. Environ. Toxicol. 28, 76–86 (2013)CrossRefGoogle Scholar
  84. 84.
    Donaldson, K., Tran, C.L.: An introduction to the short-term toxicology of respirable industrial fibres. Mutat. Res. 553, 5–9 (2004)CrossRefGoogle Scholar
  85. 85.
    Schins, R.P., Knaapen, A.M.: Genotoxicity of poorly soluble particles. Inhal. Toxicol. 19(Suppl 1), 189–198 (2007)CrossRefGoogle Scholar
  86. 86.
    Krug, H.F., Wick, P.: Nanotoxicology: an interdisciplinary challenge. Angew. Chem. Int. Ed. Engl. (2011)Google Scholar
  87. 87.
    Paur, H.R., Cassee, F.R., Teeguarden, J.G., Fissan, H., Diabate, S., Aufderheide, M., et al.: In-vitro cell exposure studies for the assessment of nanoparticle toxicity in the lung—A dialog between aerosol science and biology. J. Aerosol Sci. 42, 668–692 (2011)CrossRefADSGoogle Scholar
  88. 88.
    Lewinski, N., Colvin, V., Drezek, R.: Cytotoxicity of nanoparticles. Small 4, 26–49 (2008)CrossRefGoogle Scholar
  89. 89.
    Khalili, F.J., Jafari, S., Eghbal, M.A.: A review of molecular mechanisms involved in toxicity of nanoparticles. Adv. Pharm. Bull. 5, 447–454 (2015)CrossRefGoogle Scholar
  90. 90.
    Moller, P., Jacobsen, N.R., Folkmann, J.K., Danielsen, P.H., Mikkelsen, L., Hemmingsen, J.G., et al.: Role of oxidative damage in toxicity of particulates. Free Radic. Res. 44, 1–46 (2010)CrossRefGoogle Scholar
  91. 91.
    He, L., He, T., Farrar, S., Ji, L., Liu, T., Ma, X.: Antioxidants maintain cellular redox homeostasis by elimination of reactive oxygen species. Cell. Physiol. Biochem. 44, 532–553 (2017)CrossRefGoogle Scholar
  92. 92.
    Brown, D.M., Donaldson, K., Borm, P.J., Schins, R.P., Dehnhardt, M., Gilmour, P., et al.: Calcium and ROS-mediated activation of transcription factors and TNF-alpha cytokine gene expression in macrophages exposed to ultrafine particles. Am. J. Physiol. Lung Cell. Mol. Physiol. 286, 344–353 (2004)CrossRefGoogle Scholar
  93. 93.
    Rahman, I., MacNee, W.: Oxidative stress and regulation of glutathione in lung inflammation. Eur. Respir. J. 16, 534–554 (2000)CrossRefGoogle Scholar
  94. 94.
    Manke, A., Wang, L., Rojanasakul, Y.: Mechanisms of nanoparticle-induced oxidative stress and toxicity. Biomed. Res. Int. 2013, 942916 (2013)CrossRefGoogle Scholar
  95. 95.
    Sarkar, A., Ghosh, M., Sil, P.C.: Nanotoxicity: oxidative stress mediated toxicity of metal and metal oxide nanoparticles. J. Nanosci. Nanotechnol. 14, 730–743 (2014)CrossRefGoogle Scholar
  96. 96.
    Nel, A., Xia, T., Madler, L., Li, N.: Toxic potential of materials at the nanolevel. Science (New York, N Y) 311, 622–627 (2006)CrossRefADSGoogle Scholar
  97. 97.
    Marano, F., Hussain, S., Rodrigues-Lima, F., Baeza-Squiban, A., Boland, S.: Nanoparticles: molecular targets and cell signalling. Arch. Toxicol. 85, 733–741 (2011)CrossRefGoogle Scholar
  98. 98.
    DeForge, L.E., Preston, A.M., Takeuchi, E., Kenney, J., Boxer, L.A., Remick, D.G.: Regulation of interleukin 8 gene expression by oxidant stress. J. Biol. Chem. 268, 25568–25576 (1993)Google Scholar
  99. 99.
    Jimenez, L.A., Drost, E.M., Gilmour, P.S., Rahman, I., Antonicelli, F., Ritchie, H., et al.: PM(10)-exposed macrophages stimulate a proinflammatory response in lung epithelial cells via TNF-alpha. Am. J. Physiol. Lung Cell. Mol. Physiol. 282, L237–L248 (2002)CrossRefGoogle Scholar
  100. 100.
    Timmermann, M., Hogger, P.: Oxidative stress and 8-iso-prostaglandin F(2alpha) induce ectodomain shedding of CD163 and release of tumor necrosis factor-alpha from human monocytes. Free Radic. Biol. Med. 39, 98–107 (2005)CrossRefGoogle Scholar
  101. 101.
    Elsabahy, M., Wooley, K.L.: Cytokines as biomarkers of nanoparticle immunotoxicity. Chem. Soc. Rev. 42, 5552–5576 (2013)CrossRefGoogle Scholar
  102. 102.
    Dagenais, M., Skeldon, A., Saleh, M.: The inflammasome: in memory of Dr. Jurg Tschopp. Cell. Death Differ. 19, 5–12 (2012)CrossRefGoogle Scholar
  103. 103.
    Sharma, D., Kanneganti, T.D.: The cell biology of inflammasomes: mechanisms of inflammasome activation and regulation. J. Cell Biol. 213, 617–629 (2016)CrossRefGoogle Scholar
  104. 104.
    Rabolli, V., Lison, D., Huaux, F.: The complex cascade of cellular events governing inflammasome activation and IL-1beta processing in response to inhaled particles. Part. Fibre Toxicol. 13, 40 (2016)CrossRefGoogle Scholar
  105. 105.
    Boraschi, D., Italiani, P.: From antigen delivery system to adjuvanticy: the board application of nanoparticles in vaccinology. Vaccines (Basel) 3, 930–939 (2015)CrossRefGoogle Scholar
  106. 106.
    Yazdi, A.S., Guarda, G., Riteau, N., Drexler, S.K., Tardivel, A., Couillin, I., et al.: Nanoparticles activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome and cause pulmonary inflammation through release of IL-1alpha and IL-1beta. Proc. Natl. Acad. Sci. U.S.A. 107, 19449–19454 (2010)CrossRefADSGoogle Scholar
  107. 107.
    Dostert, C., Petrilli, V., Van, B.R., Steele, C., Mossman, B.T., Tschopp, J.: Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science (New York, N Y) 320, 674–677 (2008)CrossRefADSGoogle Scholar
  108. 108.
    Nabiev, I., Mitchell, S., Davies, A., Williams, Y., Kelleher, D., Moore, R., et al.: Nonfunctionalized nanocrystals can exploit a cell’s active transport machinery delivering them to specific nuclear and cytoplasmic compartments. Nano Lett. 7, 3452–3461 (2007)CrossRefADSGoogle Scholar
  109. 109.
    Cheng, C., Muller, K.H., Koziol, K.K., Skepper, J.N., Midgley, P.A., Welland, M.E., et al.: Toxicity and imaging of multi-walled carbon nanotubes in human macrophage cells. Biomaterials 30, 4152–4160 (2009)CrossRefGoogle Scholar
  110. 110.
    Sargent, L.M., Hubbs, A.F., Young, S.H., Kashon, M.L., Dinu, C.Z., Benkovic, S.A., et al.: Single-walled carbon nanotube-induced mitotic disruption. Mutat. Res. 745, 28–37 (2012)CrossRefGoogle Scholar
  111. 111.
    van Berol, D., Clift, M.J., Albrecht, C., Schins, R.P.: Carbon nanotubes: an insight into the mechanisms of their potential genotoxicity. Swiss Med. Wkly 142, w13698 (2012)Google Scholar
  112. 112.
    Xia, T., Kovochich, M., Liong, M., Madler, L., Gilbert, B., Shi, H., et al.: Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties. ACS Nano 2, 2121–2134 (2008)CrossRefGoogle Scholar
  113. 113.
    Singh, N., Manshian, B., Jenkins, G.J., Griffiths, S.M., Williams, P.M., Maffeis, T.G., et al.: NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. Biomaterials 30, 3891–3914 (2009)CrossRefGoogle Scholar
  114. 114.
    Magdolenova, Z., Collins, A., Kumar, A., Dhawan, A., Stone, V., Dusinska, M.: Mechanisms of genotoxicity. A review of in vitro and in vivo studies with engineered nanoparticles. Nanotoxicology 8, 233–278 (2014)Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Barbara Rothen-Rutishauser
    • 1
    Email author
  • Joël Bourquin
    • 1
  • Alke Petri-Fink
    • 1
    • 2
  1. 1.BioNanomaterials, Adolphe Merkle InstituteFribourgSwitzerland
  2. 2.Department of ChemistryUniversity of FribourgFribourgSwitzerland

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