Skip to main content

Mechanisms of Uptake and Translocation of Nanomaterials in the Lung

  • Chapter
  • First Online:
Cellular and Molecular Toxicology of Nanoparticles

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1048))

Abstract

Nanomaterials are invading our environment due to their increasing use in a very broad range of sectors making human exposure foreseeable during the life cycle of these materials. Inhalation is one of the most frequent routes of exposure in case of unintentional exposure and the small size of nanomaterials allows them to reach the deep lung. Understanding the fate and effects of nanomaterials is a great challenge for scientists as they exhibit a huge physico-chemical diversity that drives their biological reactivity. It is critical to determine the fate of nanomaterials at their route of entry in the organism as this will determine their local and/or systemic effects. In this review we will describe the epithelial barriers and the clearance processes of the respiratory tract. The mechanisms involved in the internalization of nanomaterials by respiratory cells and their ability to cross the epithelial barrier will be presented, highlighting methodologies and the role of the nanomaterial physico-chemical properties.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Stone V, Miller MR, Clift MJ et al (2016) Nanomaterials vs ambient ultrafine particles: an opportunity to exchange toxicology knowledge. Environ Health Perspect. https://doi.org/10.1289/EHP424

  2. MPPD, Multiple-Path Particle Dosimetry Model (n.d) (MPPD v 3.04) https://www.ara.com/products/multiple-path-particle-dosimetry-model-mppd-v-304

  3. Doherty GJ, McMahon HT (2009) Mechanisms of endocytosis. Annu Rev Biochem 78:857–902

    Article  CAS  PubMed  Google Scholar 

  4. Roiter Y, Ornatska M, Rammohan AR et al (2009) Interaction of lipid membrane with nanostructured surfaces. Langmuir 25(11):6287–6299

    Article  CAS  PubMed  Google Scholar 

  5. Vranic S, Garcia-Verdugo I, Darnis C et al (2013) Internalization of SiO2 nanoparticles by alveolar macrophages and lung epithelial cells and its modulation by the lung surfactant substitute Curosurf. Environ Sci Pollut Res Int 20(5):2761–2770

    Article  CAS  PubMed  Google Scholar 

  6. Vranic S, Boggetto N, Contremoulins V et al (2013) Deciphering the mechanisms of cellular uptake of engineered nanoparticles by accurate evaluation of internalization using imaging flow cytometry. Part Fibre Toxicol 10:2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Astolfo A, Arfelli F, Schültke E et al (2013) A detailed study of gold-nanoparticle loaded cells using X-ray based techniques for cell-tracking applications with single-cell sensitivity. Nanoscale 5(8):3337–3345

    Article  CAS  PubMed  Google Scholar 

  8. Drescher D, Kneipp J (2012) Nanomaterials in complex biological systems: insights from Raman spectroscopy. Chem Soc Rev 41(17):5780–5799

    Article  CAS  PubMed  Google Scholar 

  9. Vercauteren D, Vandenbroucke RE, Jones AT et al (2010) The use of inhibitors to study endocytic pathways of gene carriers: optimization and pitfalls. Mol Ther 18(3):561–569

    Article  CAS  PubMed  Google Scholar 

  10. Ivanov AI (2008) Pharmacological inhibition of endocytic pathways: is it specific enough to be useful? Methods Mol Biol 440:15–33

    Article  CAS  PubMed  Google Scholar 

  11. Brandenberger C, Mühlfeld C, Ali Z et al (2010) Quantitative evaluation of cellular uptake and trafficking of plain and polyethylene glycol-coated gold nanoparticles. Small 6(15):1669–1678

    Article  CAS  PubMed  Google Scholar 

  12. Thorley AJ, Ruenraroengsak P, Potter TE et al (2014) Critical determinants of uptake and translocation of nanoparticles by the human pulmonary alveolar epithelium. ACS Nano 8(11):11778–11789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bohmer N, Jordan A (2015) Caveolin-1 and CDC42 mediated endocytosis of silica-coated iron oxide nanoparticles in HeLa cells. Beilstein J Nanotechnol 6:167–176

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kasper J, Hermanns MI, Bantz C et al (2013) Flotillin-involved uptake of silica nanoparticles and responses of an alveolar-capillary barrier in vitro. Eur J Pharm Biopharm 84(2):275–287

    Article  CAS  PubMed  Google Scholar 

  15. Rothen-Rutishauser BM, Schürch S, Haenni B et al (2006) Interaction of fine particles and nanoparticles with red blood cells visualized with advanced microscopic techniques. Environ Sci Technol 40(14):4353–4359

    Article  CAS  PubMed  Google Scholar 

  16. Zhao Y, Sun X, Zhang G et al (2011) Interaction of mesoporous silica nanoparticles with human red blood cell membranes: size and surface effects. ACS Nano 5(2):1366–1375

    Article  CAS  PubMed  Google Scholar 

  17. Hussain S, Thomassen LC, Ferecatu I et al (2010) Carbon black and titanium dioxide nanoparticles elicit distinct apoptotic pathways in bronchial epithelial cells. Part Fibre Toxicol 7:10

    Article  PubMed  PubMed Central  Google Scholar 

  18. Nabeshi H, Yoshikawa T, Arimori A et al (2011) Effect of surface properties of silica nanoparticles on their cytotoxicity and cellular distribution in murine macrophages. Nanoscale Res Lett 6(1):93

    Article  PubMed  PubMed Central  Google Scholar 

  19. Fröhlich E (2012) The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int J Nanomedicine 7:5577–5591

    Article  PubMed  PubMed Central  Google Scholar 

  20. Kirch J, Guenther M, Doshi N et al (2012) Mucociliary clearance of micro- and nanoparticles is independent of size, shape and charge – an ex vivo and in silico approach. J Control Release 159(1):128–134

    Article  CAS  PubMed  Google Scholar 

  21. Florez L, Herrmann C, Cramer JM et al (2012) How shape influences uptake: interactions of anisotropic polymer nanoparticles and human mesenchymal stem cells. Small 8(14):2222–2230

    Article  CAS  PubMed  Google Scholar 

  22. Meng H, Yang S, Li Z et al (2011) Aspect ratio determines the quantity of mesoporous silica nanoparticle uptake by a small GTPase-dependent macropinocytosis mechanism. ACS Nano 5(6):4434–4447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Donaldson K, Murphy FA, Duffin R et al (2010) Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesothelioma. Part Fibre Toxicol 7:5

    Article  PubMed  PubMed Central  Google Scholar 

  24. Zhang B, Feng X, Yin H et al (2017) Anchored but not internalized: shape dependent endocytosis of nanodiamond. Sci Rep 7:46462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Mura S, Hillaireau H, Nicolas J et al (2011) Biodegradable nanoparticles meet the bronchial airway barrier: how surface properties affect their interaction with mucus and epithelial cells. Biomacromolecules 12(11):4136–4143

    Article  CAS  PubMed  Google Scholar 

  26. Ruge CA, Schaefer UF, Herrmann J et al (2012) The interplay of lung surfactant proteins and lipids assimilates the macrophage clearance of nanoparticles. PLoS One 7(7):e40775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. McKenzie Z, Kendall M, Mackay RM et al (2015) Surfactant protein A (SP-A) inhibits agglomeration and macrophage uptake of toxic amine modified nanoparticles. Nanotoxicology 9(8):952–962

    Article  PubMed  PubMed Central  Google Scholar 

  28. Shaw CA, Mortimer GM, Deng ZJ et al (2016) Protein corona formation in bronchoalveolar fluid enhances diesel exhaust nanoparticle uptake and pro-inflammatory responses in macrophages. Nanotoxicology 10(7):981–991

    Article  CAS  PubMed  Google Scholar 

  29. Vranic S, Gosens I, Jacobsen NR et al (2017) Impact of serum as a dispersion agent for in vitro and in vivo toxicological assessments of TiO2 nanoparticles. Arch Toxicol 91(1):353–363

    Article  CAS  PubMed  Google Scholar 

  30. Braakhuis HM, Park MV, Gosens I et al (2014) Physicochemical characteristics of nanomaterials that affect pulmonary inflammation. Part Fibre Toxicol 11:18

    Article  PubMed  PubMed Central  Google Scholar 

  31. Churg A, Brauer M, del Carmen A-CM et al (2003) Chronic exposure to high levels of particulate air pollution and small airway remodeling. Environ Health Perspect 111(5):714–718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Setyawati MI, Tay CY, Chia SL et al (2013) TiO2 nanomaterials cause endothelial cells leakiness by disrupting the homophilic interaction of VE-cadherin. Nat Commun 4:1673

    Article  CAS  PubMed  Google Scholar 

  33. Geys J, Nemery B, Hoet PH (2007) Optimisation of culture conditions to develop an in vitro pulmonary permeability model. Toxicol In Vitro 21(7):1215–1219

    Article  CAS  PubMed  Google Scholar 

  34. George I, Vranic S, Boland S et al (2015) Development of an in vitro model of human bronchial epithelial barrier to study nanoparticle translocation. Toxicol In Vitro 29(1):51–58

    Article  CAS  PubMed  Google Scholar 

  35. Bachler G, Losert S, Umehara Y et al (2015) Translocation of gold nanoparticles across the lung epithelial tissue barrier: Combining in vitro and in silico methods to substitute in vivo experiments. Part Fibre Toxicol 12:18

    Article  PubMed  PubMed Central  Google Scholar 

  36. Kemp SJ, Thorley AJ, Gorelik J et al (2008) Immortalization of human alveolar epithelial cells to investigate nanoparticle uptake. Am J Respir Cell Mol Biol 39(5):591–597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Geys J, Coenegrachts L, Vercammen J et al (2006) In vitro study of the pulmonary translocation of nanoparticles: a preliminary study. Toxicol Lett 160(3):218–226

    Article  CAS  PubMed  Google Scholar 

  38. George I, Naudin G, Boland S et al (2015) Metallic oxide nanoparticle translocation across the human bronchial epithelial barrier. Nanoscale 7(10):4529–4544

    Article  CAS  PubMed  Google Scholar 

  39. Cohen JM, Derk R, Wang L et al (2014) Tracking translocation of industrially relevant engineered nanomaterials (ENMs) across alveolar epithelial monolayers in vitro. Nanotoxicology 1:216–225

    Article  Google Scholar 

  40. Kreyling WG, Semmler-Behnke M, Takenaka S et al (2013) Differences in the biokinetics of inhaled nano- versus micrometer-sized particles. Acc Chem Res 46(3):714–722

    Article  CAS  PubMed  Google Scholar 

  41. Nemmar A, Hoet PH, Vanquickenborne B et al (2002) Passage of inhaled particles into the blood circulation in humans. Circulation 105(4):411–414

    Article  CAS  PubMed  Google Scholar 

  42. Mills NL, Amin N, Robinson SD et al (2006) Do inhaled carbon nanoparticles translocate directly into the circulation in humans? Am J Respir Crit Care Med 173(4):426–431

    Article  PubMed  Google Scholar 

  43. Wiebert P, Sanchez-Crespo A, Falk R et al (2006) No significant translocation of inhaled 35-nm carbon particles to the circulation in humans. Inhal Toxicol 18(10):741–747

    Article  CAS  PubMed  Google Scholar 

  44. Nemmar A, Vanbilloen H, Hoylaerts MF et al (2001) Passage of intratracheally instilled ultrafine particles from the lung into the systemic circulation in hamster. A J Respir Crit Care Med 164:1666–1668

    Google Scholar 

  45. Kreyling WG, Semmler-Behnke M, Seitz J et al (2009) Size dependence of the translocation of inhaled iridium and carbon nanoparticle aggregates from the lung of rats to the blood and secondary target organs. Inhal Toxicol Suppl 1:55–60

    Article  Google Scholar 

  46. Choi HS, Ashitate Y, Lee JH et al (2010) Rapid translocation of nanoparticles from the lung airspaces to the body. Nat Biotechnol 28(12):1300–1304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Elder A, Gelein R, Silva V et al (2006) Translocation of inhaled ultrafine manganese oxide particles to the central nervous system. Environ Health Perspect 114(8):1172–1178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Abid A D, Anderson D S, Das G K et al (2013) Novel lanthanide-labeled metal oxide nanoparticles improve the measurement of in vivo clearance and translocation. Part Fibre Toxicol 0:1

    Google Scholar 

  49. Shinohara N, Osima Y, Kobayashi T et al (2015) Pulmonary clearance kinetics and extrapulmonary translocation of seven titanium dioxide nano- and submicron materials following intratracheal administration in rats. Nanotoxicology 9(8):1050–1058

    Article  PubMed  Google Scholar 

  50. Kreyling WG, Semmler M, Erbe F et al (2002) Translocation of ultrafine insoluble iridium particles from lung epithelium to extrapulmonary organs is size dependent but very low. J Toxicol Environ Health A 65(20):1513–1530

    Article  CAS  PubMed  Google Scholar 

  51. Semmler M, Seitz J, Erbe F et al (2004) Long-term clearance kinetics of inhaled ultrafine insoluble iridium particles from the rat lung, including transient translocation into secondary organs. Inhal Toxicol 16(6–7):453–459

    Article  CAS  PubMed  Google Scholar 

  52. Lipka J, Semmler-Behnke M, Sperling RA et al (2010) Biodistribution of PEG-modified gold nanoparticles following intratracheal instillation and intravenous injection. Biomaterials 31(25):6574–6581

    Article  CAS  PubMed  Google Scholar 

  53. Geiser M, Stoeger T, Casaulta M et al (2014) Biokinetics of nanoparticles and susceptibility to particulate exposure in a murine model of cystic fibrosis. Part Fibre Toxicol 11:19

    Article  PubMed  PubMed Central  Google Scholar 

  54. Konduru NV, Jimenez RJ, Swami A et al (2015) Silica coating influences the corona and biokinetics of cerium oxide nanoparticles. Part Fibre Toxicol 12:31

    Article  PubMed  PubMed Central  Google Scholar 

  55. Kreyling WG, Hirn S, Möller W et al (2014) Air-blood barrier translocation of tracheally instilled gold nanoparticles inversely depends on particle size. ACS Nano 8(1):222–233

    Article  CAS  PubMed  Google Scholar 

  56. Sarlo K, Blackburn KL, Clark ED et al (2009) Tissue distribution of 20 nm, 100 nm and 1000nm fluorecent polystryrene latex nanospheres following acute systemic or acute and repeat aiway exposure in the rat. Toxicology (263):117–126

    Google Scholar 

  57. Kreyling WG (2016) Discovery of unique and ENM- specific pathophysiologic pathways: Comparison of the translocation of inhaled iridium nanoparticles from nasal epithelium versus alveolar epithelium towards the brain of rats. Toxicol Appl Pharmacol 299:41–46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Oberdorster G, Sharp Z, Atudorei V et al (2004) Translocation of inhaled ultrafine particles to the brain. Inhal Toxicol 16:437–445

    Article  CAS  PubMed  Google Scholar 

  59. Garbuzenko OB, Winkler J, Tomassone MS et al (2014) Biodegradable Janus Nanoparticles for local pulmonary delivery of hydrophilic and hydrophobic molecules to the lungs. Langmuir:12941–12949

    Google Scholar 

  60. Konduru N, Keller J, Ma-Hock L et al (2014) Biokinetics and effects of barium sulfate nanoparticles. Part Fibre Toxicol 11:55

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Armelle Baeza-Squiban .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 The Author(s)

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Puisney, C., Baeza-Squiban, A., Boland, S. (2018). Mechanisms of Uptake and Translocation of Nanomaterials in the Lung. In: Saquib, Q., Faisal, M., Al-Khedhairy, A., Alatar, A. (eds) Cellular and Molecular Toxicology of Nanoparticles. Advances in Experimental Medicine and Biology, vol 1048. Springer, Cham. https://doi.org/10.1007/978-3-319-72041-8_2

Download citation

Publish with us

Policies and ethics