Skip to main content
SpringerLink
Log in
Book cover

Cellular and Molecular Toxicology of Nanoparticles pp 59–69Cite as

The Toxicity of Nanoparticles to Human Endothelial Cells

  • Chapter
  • First Online:

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

Abstract

The use of nanoparticles (NPs) in commercially available products and as biomedicinal materials could lead to increasing contact of human blood vessels with NPs, and it is necessary to assess the potential adverse effects of NPs to cells lining blood vessels. Of them, endothelial cells (ECs) are of particular relevance as they play a crucial role in the regulation of function of blood vessels. In this book chapter, I discussed studies that used human ECs to study the toxicity and mechanisms of NPs. It has been shown that exposure of human ECs to NPs could lead to cytotoxicity, genotoxicity, endothelial activation and impaired NO signaling. Oxidative stress and inflammation induced by NPs have been suggested as the mechanisms associated with the toxicity of NPs to ECs, and a three-tier model has been proposed to explain the association between NP induced oxidative stress and toxicity. In recent years, dysfunction of autophagy (excessive autophagy induction) has also been suggested as one of the mechanisms associated with the toxicity of NPs to human ECs. In the future, it is necessary to use human ECs to assess the toxicity of NPs to better understand the potential adverse effects of NPs entering circulation.

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

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

Learn about institutional subscriptions

References

  1. European Commission Commission recommendation of 18 October 2011 on the definition of nanomaterial text with EEA relevance. http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:32011H0696. Accessed 18 Dec 2011

  2. Donaldson K, Tran L, Jimenez LA et al (2005) Combustion-derived nanoparticles: a review of their toxicology following inhalation exposure. Part Fibre Toxicol 2:10

    Article  PubMed  PubMed Central  Google Scholar 

  3. Donaldson K, Duffin R, Langrish JP et al (2013) Nanoparticles and the cardiovascular system: a critical review. Nanomedicine (Lond) 8:403–423

    Article  CAS  Google Scholar 

  4. Vance ME, Kuiken T, Vejerano EP et al (2015) Nanotechnology in the real world: redeveloping the nanomaterial consumer products inventory. Beilstein J Nanotechnol 6:1769–1780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Wong BS, Yoong SL, Jagusiak A et al (2013) Carbon nanotubes for delivery of small molecule drugs. Adv Drug Deliv Rev 65:1964–2015

    Article  CAS  PubMed  Google Scholar 

  6. Wei L, Lu J, Xu H et al (2015) Silver nanoparticles: synthesis, properties, and therapeutic applications. Drug Discov Today 20:595–601

    Article  CAS  PubMed  Google Scholar 

  7. Khan ST, Musarrat J, Al-Khedhairy AA (2016) Countering drug resistance, infectious diseases, and sepsis using metal and metal oxides nanoparticles: current status. Colloids Surf B: Biointerfaces 146:70–83

    Article  CAS  PubMed  Google Scholar 

  8. Soenen SJ, Parak WJ, Rejman J et al (2015) (Intra)cellular stability of inorganic nanoparticles: effects on cytotoxicity, particle functionality, and biomedical applications. Chem Rev 115:2109–2135

    Article  CAS  PubMed  Google Scholar 

  9. Setyawati MI, Tay CY, Docter D et al (2015) Understanding and exploiting nanoparticles’ intimacy with the blood vessel and blood. Chem Soc Rev 44:8174–8199

    Article  CAS  PubMed  Google Scholar 

  10. Libby P (2012) Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol 32:2045–2051

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Karbach S, Wenzel P, Waisman A et al (2014) eNOS uncoupling in cardiovascular diseases – the role of oxidative stress and inflammation. Curr Pharm Des 20:3579–3594

    Article  CAS  PubMed  Google Scholar 

  12. Gimbrone MA Jr, Garcia-Cardena G (2016) Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res 118:620–636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Saptarshi SR, Duschl A, Lopata AL (2015) Biological reactivity of zinc oxide nanoparticles with mammalian test systems: an overview. Nanomedicine (Lond) 10:2075–2092

    Article  CAS  Google Scholar 

  14. Sun J, Wang S, Zhao D et al (2011) Cytotoxicity, permeability, and inflammation of metal oxide nanoparticles in human cardiac microvascular endothelial cells: cytotoxicity, permeability, and inflammation of metal oxide nanoparticles. Cell Biol Toxicol 27:333–342

    Article  PubMed  Google Scholar 

  15. Liang S, Sun K, Wang Y et al (2016) Role of Cyt-C/caspases-9,3, Bax/Bcl-2 and the FAS death receptor pathway in apoptosis induced by zinc oxide nanoparticles in human aortic endothelial cells and the protective effect by alpha-lipoic acid. Chem Biol Interact 258:40–51

    Article  CAS  PubMed  Google Scholar 

  16. Gong Y, Ji Y, Liu F et al (2017) Cytotoxicity, oxidative stress and inflammation induced by ZnO nanoparticles in endothelial cells: interaction with palmitate or lipopolysaccharide. J Appl Toxicol 87:895–901

    Article  Google Scholar 

  17. Gu Y, Cheng S, Chen G et al (2017) The effects of endoplasmic reticulum stress inducer thapsigargin on the toxicity of ZnO or TiO2 nanoparticles to human endothelial cells. Toxicol Mech Methods 27:191–200

    Article  CAS  PubMed  Google Scholar 

  18. Guo H, Zhang J, Boudreau M et al (2016) Intravenous administration of silver nanoparticles causes organ toxicity through intracellular ROS-related loss of inter-endothelial junction. Part Fibre Toxicol 13:21

    Article  PubMed  PubMed Central  Google Scholar 

  19. Danielsen PH, Cao Y, Roursgaard M et al (2015) Endothelial cell activation, oxidative stress and inflammation induced by a panel of metal-based nanomaterials. Nanotoxicology 9:813–824

    Article  PubMed  Google Scholar 

  20. Yan M, Zhang Y, Xu K et al (2011) An in vitro study of vascular endothelial toxicity of CdTe quantum dots. Toxicology 282:94–103

    Article  CAS  PubMed  Google Scholar 

  21. Yang L, Yan Q, Zhao J et al (2013) The role of potassium channel in silica nanoparticle-induced inflammatory effect in human vascular endothelial cells in vitro. Toxicol Lett 223:16–24

    Article  CAS  PubMed  Google Scholar 

  22. Guo C, Yang M, Jing L et al (2016) Amorphous silica nanoparticles trigger vascular endothelial cell injury through apoptosis and autophagy via reactive oxygen species-mediated MAPK/Bcl-2 and PI3K/Akt/mTOR signaling. Int J Nanomedicine 11:5257–5276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Walker VG, Li Z, Hulderman T et al (2009) Potential in vitro effects of carbon nanotubes on human aortic endothelial cells. Toxicol Appl Pharmacol 236:319–328

    Article  CAS  PubMed  Google Scholar 

  24. Orecna M, De Paoli SH, Janouskova O et al (2014) Toxicity of carboxylated carbon nanotubes in endothelial cells is attenuated by stimulation of the autophagic flux with the release of nanomaterial in autophagic vesicles. Nanomedicine 10:939–948

    Article  CAS  PubMed  Google Scholar 

  25. Ge C, Du J, Zhao L et al (2011) Binding of blood proteins to carbon nanotubes reduces cytotoxicity. Proc Natl Acad Sci U S A 108:16968–16973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Matuszak J, Baumgartner J, Zaloga J et al (2016) Nanoparticles for intravascular applications: physicochemical characterization and cytotoxicity testing. Nanomedicine (Lond) 11:597–616

    Article  CAS  Google Scholar 

  27. Menard N, Tsapis N, Poirier C et al (2012) Novel surfactants with diglutamic acid polar head group: drug solubilization and toxicity studies. Pharm Res 29:1882–1896

    Article  CAS  PubMed  Google Scholar 

  28. Liu F, Huang H, Gong Y et al (2017) Evaluation of in vitro toxicity of polymeric micelles to human endothelial cells under different conditions. Chem Biol Interact 263:46–54

    Article  CAS  PubMed  Google Scholar 

  29. Su Y, Zhao L, Meng F et al (2017) Silver nanoparticles decorated lipase-sensitive polyurethane micelles for on-demand release of silver nanoparticles. Colloids Surf B: Biointerfaces 152:238–244

    Article  CAS  PubMed  Google Scholar 

  30. Moller P, Hemmingsen JG, Jensen DM et al (2015) Applications of the comet assay in particle toxicology: air pollution and engineered nanomaterials exposure. Mutagenesis 30:67–83

    Article  PubMed  Google Scholar 

  31. Bayat N, Lopes VR, Scholermann J et al (2015) Vascular toxicity of ultra-small TiO2 nanoparticles and single walled carbon nanotubes in vitro and in vivo. Biomaterials 63:1–13

    Article  CAS  PubMed  Google Scholar 

  32. Duan J, Yu Y, Li Y et al (2013) Toxic effect of silica nanoparticles on endothelial cells through DNA damage response via Chk1-dependent G2/M checkpoint. PLoS One 8:e62087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Frikke-Schmidt H, Roursgaard M, Lykkesfeldt J et al (2011) Effect of vitamin C and iron chelation on diesel exhaust particle and carbon black induced oxidative damage and cell adhesion molecule expression in human endothelial cells. Toxicol Lett 203:181–189

    Article  CAS  PubMed  Google Scholar 

  34. Calarco A, Bosetti M, Margarucci S et al (2013) The genotoxicity of PEI-based nanoparticles is reduced by acetylation of polyethylenimine amines in human primary cells. Toxicol Lett 218:10–17

    Article  CAS  PubMed  Google Scholar 

  35. Cowie H, Magdolenova Z, Saunders M et al (2015) Suitability of human and mammalian cells of different origin for the assessment of genotoxicity of metal and polymeric engineered nanoparticles. Nanotoxicology 9(1):57–65

    Article  CAS  PubMed  Google Scholar 

  36. Xu Y, Wang SY, Yang J et al (2013) Multiwall carbon nano-onions induce DNA damage and apoptosis in human umbilical vein endothelial cells. Environ Toxicol 28:442–450

    Article  CAS  PubMed  Google Scholar 

  37. Soenen SJ, Montenegro JM, Abdelmonem AM et al (2014) The effect of nanoparticle degradation on amphiphilic polymer-coated quantum dot toxicity: the importance of particle functionality assessment in toxicology [corrected]. Acta Biomater 10:732–741

    Article  CAS  PubMed  Google Scholar 

  38. Guo YY, Zhang J, Zheng YF et al (2011) Cytotoxic and genotoxic effects of multi-wall carbon nanotubes on human umbilical vein endothelial cells in vitro. Mutat Res 721:184–191

    Article  CAS  PubMed  Google Scholar 

  39. Zhu MT, Wang B, Wang Y et al (2011) Endothelial dysfunction and inflammation induced by iron oxide nanoparticle exposure: risk factors for early atherosclerosis. Toxicol Lett 203:162–171

    Article  CAS  PubMed  Google Scholar 

  40. Montiel-Davalos A, Ventura-Gallegos JL, Alfaro-Moreno E et al (2012) TiO(2) nanoparticles induce dysfunction and activation of human endothelial cells. Chem Res Toxicol 25:920–930

    Article  CAS  PubMed  Google Scholar 

  41. Li CH, Liao PL, Shyu MK et al (2012) Zinc oxide nanoparticles-induced intercellular adhesion molecule 1 expression requires Rac1/Cdc42, mixed lineage kinase 3, and c-Jun N-terminal kinase activation in endothelial cells. Toxicol Sci 126:162–172

    Article  PubMed  Google Scholar 

  42. Shi J, Sun X, Lin Y et al (2014) Endothelial cell injury and dysfunction induced by silver nanoparticles through oxidative stress via IKK/NF-kappaB pathways. Biomaterials 35:6657–6666

    Article  CAS  PubMed  Google Scholar 

  43. Cao Y, Jacobsen NR, Danielsen PH et al (2014) Vascular effects of multiwalled carbon nanotubes in dyslipidemic ApoE−/− mice and cultured endothelial cells. Toxicol Sci 138:104–116

    Article  CAS  PubMed  Google Scholar 

  44. Cao Y, Roursgaard M, Danielsen PH et al (2014) Carbon black nanoparticles promote endothelial activation and lipid accumulation in macrophages independently of intracellular ROS production. PLoS One 9:e106711

    Article  PubMed  PubMed Central  Google Scholar 

  45. Napierska D, Thomassen LC, Vanaudenaerde B et al (2012) Cytokine production by co-cultures exposed to monodisperse amorphous silica nanoparticles: the role of size and surface area. Toxicol Lett 211:98–104

    Article  CAS  PubMed  Google Scholar 

  46. Snyder-Talkington BN, Schwegler-Berry D, Castranova V et al (2013) Multi-walled carbon nanotubes induce human microvascular endothelial cellular effects in an alveolar-capillary co-culture with small airway epithelial cells. Part Fibre Toxicol 10:35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Sisler JD, Pirela SV, Friend S et al (2015) Small airway epithelial cells exposure to printer-emitted engineered nanoparticles induces cellular effects on human microvascular endothelial cells in an alveolar-capillary co-culture model. Nanotoxicology 9:769–779

    Article  CAS  PubMed  Google Scholar 

  48. Cao Y, Roursgaard M, Jacobsen NR et al (2016) Monocyte adhesion induced by multi-walled carbon nanotubes and palmitic acid in endothelial cells and alveolar-endothelial co-cultures. Nanotoxicology 10:235–244

    CAS  PubMed  Google Scholar 

  49. Duan J, Yu Y, Yu Y et al (2014) Silica nanoparticles induce autophagy and endothelial dysfunction via the PI3K/Akt/mTOR signaling pathway. Int J Nanomedicine 9:5131–5141

    Article  PubMed  PubMed Central  Google Scholar 

  50. Zhang L, Wang X, Miao Y et al (2016) Magnetic ferroferric oxide nanoparticles induce vascular endothelial cell dysfunction and inflammation by disturbing autophagy. J Hazard Mater 304:186–195

    Article  CAS  PubMed  Google Scholar 

  51. Astanina K, Simon Y, Cavelius C et al (2014) Superparamagnetic iron oxide nanoparticles impair endothelial integrity and inhibit nitric oxide production. Acta Biomater 10:4896–4911

    Article  CAS  PubMed  Google Scholar 

  52. Corbalan JJ, Medina C, Jacoby A et al (2011) Amorphous silica nanoparticles trigger nitric oxide/peroxynitrite imbalance in human endothelial cells: inflammatory and cytotoxic effects. Int J Nanomedicine 6:2821–2835

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Solarska-Sciuk K, Gajewska A, Skolimowski J et al (2013) Stimulation of production of reactive oxygen and nitrogen species in endothelial cells by unmodified and Fenton-modified ultradisperse detonation diamond. Biotechnol Appl Biochem 60:259–265

    Article  CAS  PubMed  Google Scholar 

  54. Su L, Han L, Ge F et al (2012) The effect of novel magnetic nanoparticles on vascular endothelial cell function in vitro and in vivo. J Hazard Mater 235–236:316–325

    Article  PubMed  Google Scholar 

  55. Han L, Su L, Chen D et al (2015) ZnS nanoarchitectures induced dysfunction of vascular endothelial cells in vitro and in vivo. Environ Toxicol 30:755–768

    Article  CAS  PubMed  Google Scholar 

  56. Chuang KJ, Lee KY, Pan CH et al (2016) Effects of zinc oxide nanoparticles on human coronary artery endothelial cells. Food Chem Toxicol 93:138–144

    Article  CAS  PubMed  Google Scholar 

  57. Moller P, Christophersen DV, Jacobsen NR et al (2016) Atherosclerosis and vasomotor dysfunction in arteries of animals after exposure to combustion-derived particulate matter or nanomaterials. Crit Rev Toxicol 46:437–476

    Article  PubMed  Google Scholar 

  58. Cao Y, Long J, Ji Y et al (2016) Foam cell formation by particulate matter (PM) exposure: a review. Inhal Toxicol 28:583–590

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  60. Nel A, Xia T, Meng H et al (2013) Nanomaterial toxicity testing in the 21st century: use of a predictive toxicological approach and high-throughput screening. Acc Chem Res 46:607–621

    Article  CAS  PubMed  Google Scholar 

  61. Halamoda KB, Chapuis BC, Guney-Ayra S et al (2012) Induction of oxidative stress, lysosome activation and autophagy by nanoparticles in human brain-derived endothelial cells. Biochem J 441:813–821

    Article  Google Scholar 

  62. Lai TH, Shieh JM, Tsou CJ et al (2015) Gold nanoparticles induce heme oxygenase-1 expression through Nrf2 activation and Bach1 export in human vascular endothelial cells. Int J Nanomedicine 10:5925–5939

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Guo C, Xia Y, Niu P et al (2015) Silica nanoparticles induce oxidative stress, inflammation, and endothelial dysfunction in vitro via activation of the MAPK/Nrf2 pathway and nuclear factor-kappaB signaling. Int J Nanomedicine 10:1463–1477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Liu X, Sun J (2014) Potential proinflammatory effects of hydroxyapatite nanoparticles on endothelial cells in a monocyte-endothelial cell coculture model. Int J Nanomedicine 9:1261–1273

    PubMed  PubMed Central  Google Scholar 

  65. Jiang F (2016) Autophagy in vascular endothelial cells. Clin Exp Pharmacol Physiol 43:1021–1028

    Article  CAS  PubMed  Google Scholar 

  66. Gatica D, Chiong M, Lavandero S et al (2015) Molecular mechanisms of autophagy in the cardiovascular system. Circ Res 116:456–467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Stern ST, Adiseshaiah PP, Crist RM (2012) Autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity. Part Fibre Toxicol 9:20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Manshian BB, Pfeiffer C, Pelaz B et al (2015) High-content imaging and gene expression approaches to unravel the effect of surface functionality on cellular interactions of silver nanoparticles. ACS Nano 9:10431–10444

    Article  CAS  PubMed  Google Scholar 

  69. Yang FY, Yu MX, Zhou Q et al (2012) Effects of iron oxide nanoparticle labeling on human endothelial cells. Cell Transplant 21:1805–1820

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Key Laboratory of Environment-Friendly Chemistry and Applications of Ministry Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan, People’s Republic of China

    Yi Cao

Authors
  1. Yi Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yi Cao .

Editor information

Editors and Affiliations

  1. Zoology Department, College of Sciences, King Saud University, Riyadh, Saudi Arabia

    Quaiser Saquib

  2. Department of Botany and Microbiology, College of Sciences, King Saud University, Riyadh, Saudi Arabia

    Mohammad Faisal

  3. Zoology Department, College of Sciences, King Saud University, Riyadh, Saudi Arabia

    Abdulaziz A. Al-Khedhairy

  4. Department of Botany and Microbiology, College of Sciences, King Saud University, Riyadh, Saudi Arabia

    Abdulrahman A. Alatar

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

Cao, Y. (2018). The Toxicity of Nanoparticles to Human Endothelial Cells. 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_4

Download citation

Publish with us

Policies and ethics

Search

Navigation