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Evaluation of gold nanoparticles biocompatibility: a multiparametric study on cultured endothelial cells and macrophages

  • Antonina Orlando
  • Miriam Colombo
  • Davide Prosperi
  • Fabio Corsi
  • Alice Panariti
  • Ilaria Rivolta
  • Massimo Masserini
  • Emanuela Cazzaniga
Research Paper

Abstract

Colloidal gold nanoparticles (AuNPs) have been considered an established advanced tool in biomedicine thanks to their physicochemical properties combined with nanoscale size ideal for the interrogation of biological systems. However, such properties are believed to be a possible major cause of “unsafety” of these materials. For this reason, increasing attention has been due to assess how AuNPs affect cell behaviour in cultures. In the present work, we investigate the effects of PMA polymer-coated Au@PMA PEGylated (8.9 ± 0.2 nm) or not (6.6 ± 0.6 nm) on HUVECs and macrophages, which are model cell types likely to interact with Au@PMA after systemic administration in vivo, using a multiparametric approach. Testing different NPs concentrations and incubation times, we analysed the effect of such NPs on cell viability, oxidative stress, inflammatory processes, and cell uptake. Our data suggested that Au@PMA reduced the cell viability mostly through oxidative stress and TNF-α production after the uptake by HUVECs and macrophages, respectively. PEGylation conferred improved biocompatibility to Au@PMA in particular, no significant effects on any parameter tested could be observed at a concentration of 20 µg mL−1. This approach allowed us to explore different aspects of cell-NPs interaction and to suggest that these NPs could be potentially used for the in vivo studies.

Keywords

Gold nanoparticles Endothelial cells Macrophages Oxidative stress Cellular toxicity Nanoparticle uptake Colloids Health effects 

Notes

Acknowledgments

The authors report no conflict of interest. The authors are the sole responsible for the content and writing of the paper. We thank R. Allevi (CMENA, University of Milano) for TEM images. This work was supported by Grants from FAR 2010, FAR 2011, and “The MULAN Project” from Cariplo Foundation (Grant n. 2011-2096).

Supplementary material

11051_2016_3359_MOESM1_ESM.eps (4.9 mb)
Figure SM1. Internalization of NPs as observed with TEM. HUVECs were incubated with 20 µg mL–1 of Au@PMA for 15 min (panel A and B), 1h (panel C and D) or 24 h (panel E and F). Arrowheads indicate NPs. Abbreviations: EN, endosomes; LY, lysosomes; N, nucleus. (EPS 5052 kb)
11051_2016_3359_MOESM2_ESM.eps (5 mb)
Figure SM2. Internalization of NPs as observed with TEM. HUVECs were incubated with 20 µg mL–1 of PEG-Au@PMA for 15 min (panel A and B), 1h (panel C and D) or 24 h (panel E and F). Arrowheads indicate NPs. Abbreviations: EN, endosomes; N, nucleus. (EPS 5122 kb)
11051_2016_3359_MOESM3_ESM.eps (5.2 mb)
Figure SM3. Internalization of NPs as observed with TEM. Macrophages were incubated with 20 µg mL–1 of Au@PMA for 15 min (panel A and B), 1h (panel C and D) or 24 h (panel E and F). Arrowheads indicate NPs. Abbreviations: EN, endosomes; N, nucleus. (EPS 5277 kb)
11051_2016_3359_MOESM4_ESM.eps (5.3 mb)
Figure SM4. Internalization of NPs as observed with TEM. Macrophages were incubated with 20 µg mL–1 of PEG-Au@PMA for 15 min (panel A and B), 1h (panel C and D) or 24 h (panel E and F). Arrowheads indicate NPs. Abbreviations: EN, endosomes; N, nucleus. (EPS 5383 kb)

References

  1. Afergan E, Ben David M, Epstein H et al (2010) Liposomal simvastatin attenuates neointimal hyperplasia in rats. AAPS J 12(2):181–187CrossRefGoogle Scholar
  2. Apopa PL, Qian Y, Shao R et al (2009) Iron oxide nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule remodeling. Part Fibre Toxicol 6:1. doi: 10.1186/1743-8977-6-1 CrossRefGoogle Scholar
  3. Brust M, Walker M, Bethell D et al (1994) Synthesis of thiol-derivatized gold nanoparticles in a two phase liquid-liquid system. Chem Commum 7:801–802CrossRefGoogle Scholar
  4. Bulbarelli A, Lonati E, Brambilla A et al (2012) Aβ42 production in brain capillary endothelial cells after oxygen and glucose deprivation. Mol Cell Neurosci 49:415–422CrossRefGoogle Scholar
  5. Casals E, Puntes VF (2012) Inorganic nanoparticle biomolecular corona: formation, evolution and biological impact. Nanomedicine 7:1917–1930CrossRefGoogle Scholar
  6. Cazzaniga E, Bulbarelli A, Lonati E et al (2011) Abeta peptide toxicity is reduced after treatments decreasing phosphatidylethanolamine content in differentiated neuroblastoma cells. Neurochem Res 36:863–869CrossRefGoogle Scholar
  7. Choi YH, Jin GY, Li GZ et al (2011) Cornuside suppresses lipopolysaccharide-induced inflammatory mediators by inhibiting nuclear factor-kappa B activation in RAW 264.7 macrophages. Biol Pharm Bull 34:959–966CrossRefGoogle Scholar
  8. Cohen-Sela E, Dangoor D, Epstein H et al (2006) Nanospheres of a bisphosphonate attenuate intimal hyperplasia. J Nanosci Nanotechnol 6:3226–3234CrossRefGoogle Scholar
  9. Connor EE, Mwamuka J, Gole A et al (2005) Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. Small 1:325–327CrossRefGoogle Scholar
  10. Cui W, Li J, Zhang Y et al (2012) Effects of aggregation and the surface properties of gold nanoparticles on cytotoxicity and cell growth. Nanomedicine 8:46–53Google Scholar
  11. Du L, Miao X, Jia H et al (2012) Detection of nitric oxide in macrophage cells for the assessment of the cytotoxicity of gold nanoparticles. Talanta 101:11–16CrossRefGoogle Scholar
  12. Freese C, Gibson MI, Klok HA et al (2012) Size- and coating-dependent uptake of polymer-coated gold nanoparticles in primary human dermal microvascular endothelial cells. Biomacromolecules 13:1533–1543CrossRefGoogle Scholar
  13. Lipka J, Semmler-Behnke M, Sperling RA et al (2010) Biodistribution of PEG-modified gold nanoparticles following intratracheal instillation and intravenous injection. Biomaterials 31:6574–6581CrossRefGoogle Scholar
  14. Monopoli MP, Aberg C, Salvati A, Dawson KA (2012) Biomolecular coronas provide the biological identity of nanosized materials. Nat Nanotechnol 7:779–786CrossRefGoogle Scholar
  15. Monteiro-Riviere NA, Inman AO, Zhang LW (2009) Limitations and relative utility of screening assays to assess engineered nanoparticle toxicity in a human cell line. Toxicol Appl Pharmacol 234:222–235CrossRefGoogle Scholar
  16. Orlando A, Re F, Sesana S et al (2013) Effect of nanoparticles binding β-amyloid peptide on nitric oxide production by cultured endothelial cells and macrophages. Int J Nanomed 8:1335–1347CrossRefGoogle Scholar
  17. Panariti A, Lettiero B, Alexandrescu R et al (2013) Dynamic investigation of interaction of biocompatible iron oxide nanoparticles with epithelial cells for biomedical applications. J Biomed Nanotechnnol 9:1556–1569CrossRefGoogle Scholar
  18. Pellegrino T, Manna L, Kudera S et al (2004) Hydrophobic nanocrystals coated with an amphiphilic polymer shell: a general route to water soluble nanocrystals. Nano Lett 4:703–707CrossRefGoogle Scholar
  19. Puvanakrishnan P, Park J, Chatterjee D et al (2012) In vivo tumor targeting of gold nanoparticles: effect of particle type and dosing strategy. Int J Nanomed 7:1251–1258CrossRefGoogle Scholar
  20. Soenen SJ, De Cuyper M (2010) How to assess cytotoxicity of (iron oxide-based) nanoparticles: a technical note using cationic magnetoliposomes. Contrast Media Mol Imaging 6:153–164CrossRefGoogle Scholar
  21. Sperling RA, Rivera Gil F, Zhang F et al (2008) Biological applications of gold nanoparticles. Chem Soc Rev 37:1896–1908CrossRefGoogle Scholar
  22. Zhang Q, Hitchins VM, Schrand AM et al (2011) Uptake of gold nanoparticles in murine macrophage cells without cytotoxicity or production of pro-inflammatory mediators. Nanotoxicology 5:284–295CrossRefGoogle Scholar
  23. 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 203:162–171CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Antonina Orlando
    • 1
  • Miriam Colombo
    • 2
  • Davide Prosperi
    • 2
  • Fabio Corsi
    • 3
  • Alice Panariti
    • 1
  • Ilaria Rivolta
    • 1
  • Massimo Masserini
    • 1
  • Emanuela Cazzaniga
    • 1
  1. 1.Department of Health SciencesUniversity of Milano-BicoccaMonzaItaly
  2. 2.Department of Biotechnology and BiosciencesUniversity of Milano-BicoccaMilanItaly
  3. 3.Department of Biomedical and Clinical SciencesUniversity of MilanoMilanItaly

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