Skip to main content
SpringerLink
Log in

Dynamic changes of protein corona compositions on the surface of zinc oxide nanoparticle in cell culture media

  • Research Article
  • Published:
Frontiers of Chemical Science and Engineering Aims and scope Submit manuscript

Abstract

The potential applications of nanomaterials used in nanomedicine as ingredients in drug delivery systems and in other products continue to expand. When nanomaterials are introduced into physiological environments and driven by energetics, they readily associate proteins forming a protein corona (PC) on their surface. This PC could result in an alteration of the nanomaterial’s surface characteristics, affecting their interaction with cells due to conformational changes in adsorbed protein molecules. However, our current understanding of nanobiological interactions is still very limited. Utilizing a liquid chromatography–mass spectroscopy/mass spectroscopy technology and a Cytoscape plugin (ClueGO) approach, we examined the composition of the PC for a set of zinc oxide nanoparticles (ZnONP) from cell culture media typically and further analyzed the biological interaction of identified proteins, respectively. In total, 36 and 33 common proteins were investigated as being bound to ZnONP at 5 min and 60 min, respectively. These proteins were further analyzed with ClueGO, a Cytoscape plugin, which provided gene ontology and the biological interaction processes of identified proteins. Proteins bound to the surface of nanoparticles that may modify the structure, therefore the function of the adsorbed protein could be consequently affect the complicated biological processes.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Blunk T, Hochstrasser D F, Sanchez J C, Muller B W, Muller R H. Colloidal carriers for intravenous drug targeting: Plasma protein adsorption patterns on surface-modified latex particles evaluated by two-dimensional polyacrylamide gel electrophoresis. Electrophoresis, 1993, 14(12): 1382–1387

    Article  CAS  PubMed  Google Scholar 

  2. Ehrenberg M S, Friedman A E, Finkelstein J N, Oberdorster G, McGrath J L. The influence of protein adsorption on nanoparticle association with cultured endothelial cells. Biomaterials, 2009, 30 (4): 603–610

    Article  CAS  PubMed  Google Scholar 

  3. Lundqvist M, Augustsson C, Lilja M, Lundkvist K, Dahlbäck B, Linse S, Cedervall T. The nanoparticle protein corona formed in human blood or human blood fractions. PLoS One, 2017, 12(4): e0175871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Beduneau A, Ma Z, Grotepas C B, Kabanov A, Rabinow B E, Gong N, Mosley R L, Dou H, Boska M D, Gendelman H E. Facilitated monocyte-macrophage uptake and tissue distribution of superparmagnetic iron-oxide nanoparticles. PLoS One, 2009, 4(2): e4343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Clift M J, Bhattacharjee S, Brown D M, Stone V. The effects of serum on the toxicity of manufactured nanoparticles. Toxicology Letters, 2010, 198(3): 358–365

    Article  CAS  PubMed  Google Scholar 

  6. Khanna P, Ong C, Bay B H, Baeg G H. Nanotoxicity: An interplay of oxidative stress, inflammation and cell death. Nanomaterials (Basel, Switzerland), 2015, 5(3): 1163–1180

    Article  CAS  Google Scholar 

  7. Lartigue L,Wilhelm C, Servais J, Factor C, Dencausse A, Bacri J C, Luciani N, Gazeau F. Nanomagnetic sensing of blood plasma protein interactions with iron oxide nanoparticles: Impact on macrophage uptake. ACS Nano, 2012, 6(3): 2665–2678

    Article  CAS  PubMed  Google Scholar 

  8. Lunov O, Syrovets T, Loos C, Beil J, Delacher M, Tron K, Nienhaus G U, Musyanovych A, Mailänder V, Landfester K, et al. Differential uptake of functionalized polystyrene nanoparticles by human macrophages and a monocytic cell line. ACS Nano, 2011, 5(3): 1657–1669

    Article  CAS  PubMed  Google Scholar 

  9. Walkey C D, Olsen J B, Song F, Liu R, Liu R, Guo H, Olsen D W, Cohen Y, Emili A, Chan WC. Protein corona fingerprinting predicts the cellular interaction of gold and silver nanoparticles. ACS Nano, 2014, 8(3): 2439–2455

    Article  CAS  PubMed  Google Scholar 

  10. Gu Z, Yang Z, Chong Y, Ge C, Weber J K, Bell D R, Zhou R. Surface curvature relation to protein adsorption for carbon-based nanomaterials. Scientific Reports, 2015, 5(1): 10886

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Marucco A, Gazzano E, Ghigo D, Enrico E, Fenoglio I. Fibrinogen enhances the inflammatory response of alveolar macrophages to TiO2, SiO2 and carbon nanomaterials. Nanotoxicology, 2016, 10(1): 1–9

    CAS  PubMed  Google Scholar 

  12. Ge C, Du J, Zhao L,Wang L, Liu Y, Li D, Yang Y, Zhou R, Zhao Y, Chai Z, Chen C. Binding of blood proteins to carbon nanotubes reduces cytotoxicity. Proceedings of the National Academy of Sciences of the United States of America, 2011, 108(41): 16968–16973

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hajipour M J, Raheb J, Akhavan O, Arjmand S, Mashinchian O, Rahman M, Abdolahad M, Serpooshan V, Laurentj L, Mahmoudi M. Personalized disease-specific protein corona influences the therapeutic impact of graphene oxide. Nanoscale, 2015, 7(19): 8978–8994

    Article  CAS  PubMed  Google Scholar 

  14. Salvati A, Pitek A S, Monopoli M P, Prapainop K, Bombelli F B, Hristov D R, Kelly P M, Åberg C, Mahon E, Dawson K A. Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface. Nature Nanotechnology, 2013, 8(2): 137–143

    Article  CAS  PubMed  Google Scholar 

  15. Deng Z J, Liang M, Monteiro M, Toth I, Minchin R F. Nanoparticleinduced unfolding of fibrinogen promotes Mac-1 receptor activation and inflammation. Nature Nanotechnology, 2011, 6(1): 39–44

    Article  CAS  PubMed  Google Scholar 

  16. Saikia J, Yazdimamaghani M, Hadipour M. S P, Ghandehari H. Differential protein adsorption and cellular uptake of silica nanoparticles based on size and porosity. ACS Applied Materials & Interfaces, 2016, 8(50): 34820–34832

    Article  CAS  Google Scholar 

  17. Anders C B, Eixenberger J E, Franco N A, Hermann R J, Rainey K D, Chess J J, Punnooseb A, Wingett D G. ZnO nanoparticle preparation route influences surface reactivity, dissolution and cytotoxicity. Environmental Science. Nano, 2018, 5(2): 572–588

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Rasmussen J W, Martinez E, Louka P, Denise G,Wingett D G. Zinc oxide nanoparticles for selective destruction of tumor cells and potential for drug delivery applications. Expert Opinion on Drug Delivery, 2010, 7(9): 1063–1077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Scherzad A, Meyer T, Kleinsasser N, Hackenberg S. Molecular mechanisms of zinc oxide nanoparticle-induced genotoxicity short running title: Genotoxicity of ZnO NPs. Materials (Basel), 2017, 10 (12): e1427

    Google Scholar 

  20. Singh N, Manshian B, Jenkins G J, Griffiths S M, Williams P M, Maffeis T G, Wright C J, Doak S H. Nanogenotoxicology: The DNA damaging potential of engineered nanomaterials. Biomaterials, 2009, 30(23–24): 3891–3914

    Article  CAS  PubMed  Google Scholar 

  21. Rajput V D, Minkina T M, Behal A, Sushkova S N, Mandzhieva S, Singh R, Gorovtsov A, Tsitsuashvili V S, Purvis W O, Ghazaryan K A, et al. Effects of zinc-oxide nanoparticles on soil, plants, animals and soil organisms: A review. Environmental Nanotechnology, Monitoring & Management, 2018, 9: 76–84

    Article  Google Scholar 

  22. Wahab R, Siddiqui M A, Saquib Q, Dwivedi S, Ahmad J, Musarrat J, Al-Khedhairy A A, Shin H S. ZnO nanoparticles induced oxidative stress and apoptosis in HepG2 and MCF-7 cancer cells and their antibacterial activity. Colloids and Surfaces. B, Biointerfaces, 2014, 117(1): 267–276

    Article  CAS  PubMed  Google Scholar 

  23. Chevallet M, Gallet B, Fuchs A, Jouneau P H, Um K, Mintz E, Michaud-Soret I. Metal homeostasis disruption and mitochondrial dysfunction in hepatocytes exposed to sub-toxic doses of zinc oxide nanoparticles. Nanoscale, 2016, 8(43): 18495–18506

    Article  CAS  PubMed  Google Scholar 

  24. Zhang W, Zhao Y, Li F, Li L, Feng Y, Min L, Ma D, Yu S, Liu J, Zhang H, et al. Zinc oxide nanoparticle caused plasma metabolomic perturbations correlate with hepatic steatosis. Frontiers in Pharmacology, 2018, 9: 57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Leite-Silva V R, Liu D C, Sanchez W Y, Studier H, Mohammed Y H, Holmes A, Becker W, Grice J E, Benson H A, Roberts M S. Effect of flexing and massage on in vivo human skin penetration and toxicity of zinc oxide nanoparticles. Nanomedicine (London), 2016, 11(10): 1193–1205

    Article  CAS  Google Scholar 

  26. Sayes C M, Reed K L, Warheit D B. Assessing toxicity of fine and nanoparticles: Comparing in vitro measurements to in vivo pulmonary toxicity profiles. Toxicological Sciences: An Official Journal of the Society of Toxicology, 2007, 97(1): 163–180

    Article  CAS  Google Scholar 

  27. Xia T, Zhao Y, Sager T, George S, Pokhrel S, Li N, Schoenfeld D, Meng H, Lin S,Wang X, et al. Decreased dissolution of ZnO by iron doping yields nanoparticles with reduced toxicity in the rodent lung and zebrafish embryos. ACS Nano, 2011, 5(2): 1223–1235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Warheit D B, Sayes C M, Reed K L. Nanoscale and fine zinc oxide particles: Can in vitro assays accurately forecast lung hazards following inhalation exposures? Environmental Science & Technology, 2009, 43(20): 7939–7945

    Article  CAS  Google Scholar 

  29. Giau V V, An S S. Emergence of exosomal miRNAs as a diagnostic biomarker for Alzheimer’s disease. Journal of the Neurological Sciences, 2016, 15(360): 141–152

    Article  CAS  Google Scholar 

  30. Mana M N, Fougères P A, Leung Y H, Liu F, Djurišić A B, Giesy J P, Leung K M Y. Physicochemical characteristics and toxicity of surface-modified zinc oxide nanoparticles to freshwater and marine microalgae. Scientific Reports, 2017, 7(1): 15909

    Article  CAS  Google Scholar 

  31. Milani S, Bombelli F B, Pitek A S, Dawson K A, Rädler J. Reversible versus irreversible binding of transferrin to polystyrene nanoparticles: Soft and hard corona. ACS Nano, 2012, 6(3): 2532–2541

    Article  CAS  Google Scholar 

  32. Pederzoli F, Tosi G, Vandelli M A, Belletti D, Forni F, Ruozi B. Protein corona and nanoparticles: How can we investigate on? Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology, 2017, 9(6): e1467

    Google Scholar 

  33. Rao A, Long H, Harley-Trochimczyk A, Pham T, Zettl A, Carraro C, Maboudian R. In situ localized growth of ordered metal oxide hollow sphere array on microheater platform for sensitive, ultra-fast gas sensing. ACS Applied Materials & Interfaces, 2017, 9(3): 2634–2641

    Article  CAS  Google Scholar 

  34. Schöttler S, Landfester K, Mailänder V. Controlling the stealth effect of nanocarriers through understanding the protein corona. Angewandte Chemie International Edition in English, 2016, 55(31): 8806–8815

    Article  CAS  Google Scholar 

  35. Tenzer S, Docter D, Kuharev J, Musyanovych A, Fetz V, Hecht R, Schlenk F, Fischer D, Kiouptsi K, Reinhardt C, et al. Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology. Nature Nanotechnology, 2013, 8(10): 772–781

    Article  CAS  PubMed  Google Scholar 

  36. Saha K, Rahimi M, Yazdani M, Kim S T, Moyano D F, Hou S, Das R, Mout R, Rezaee F, Mahmoudi M, et al. Regulation of macrophage recognition through the interplay of nanoparticle surface functionality and protein corona. ACS Nano, 2016, 10(4): 4421–4430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Shannahan J H, Brown J M, Chen R, Ke P C, Lai X, Mitra S, Witzmann F A. Comparison of nanotube-protein corona composition in cell culture media. Small, 2013, 9(12): 2171–2181

    Article  CAS  PubMed  Google Scholar 

  38. Shannahan J H, Lai X, Ke P C, Podila R, Brown J M, Witzmann F A. Silver nanoparticle protein corona composition in cell culture media. PLoS One, 2013, 8(9): e74001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kim K M, Choi M H, Lee J K, Jeong J, Kim Y R, Kim M K, Paek S M, Oh J M. Physicochemical properties of surface charge-modified ZnO nanoparticles with different particle sizes. International Journal of Nanomedicine, 2014, 9(Suppl 2): 41–56

    Google Scholar 

  40. Shim K H, Hulme J, Maeng E H, Kim M K. An S S A. Analysis of zinc oxide nanoparticles binding proteins in rat blood and brain homogenate. International Journal of Nanomedicine, 2014, 9(Suppl 2): 217–224

    Google Scholar 

  41. Cedervall T, Lynch I, Foy M, Berggård T, Donnelly S C, Cagney G, Linse S, Dawson K A. Detailed identification of plasma proteins adsorbed on copolymer nanoparticles. Angewandte Chemie International Edition in English, 2007, 46(30): 5754–5756

    Article  CAS  Google Scholar 

  42. Lara S, Alnasser F, Polo E, Garry D, Giudice M C L, Hristov D R, Rocks L, Salvati A, Yan Y, Dawso N K A. Identification of receptor binding to the biomolecular corona of nanoparticles. ACS Nano, 2017, 11(2): 1884–1893

    Article  CAS  PubMed  Google Scholar 

  43. Kreuter J, Shamenkov D, Petrov V, Ramge P, Cychutek K, Koch- Brandt C, Alyautdin R. Apolipoprotein-mediated transport of nanoparticle-bond drugs across the blood-brain barrier. Journal of Drug Targeting, 2002, 10(4): 317–325

    Article  CAS  PubMed  Google Scholar 

  44. Palchetti S, Colapicchioni V, Digiacomo L, Caracciolo G, Pozzi D, Capriotti A L, La Barbera G, Laganà A. The protein corona of circulating PEGylated liposomes. Biochimica et Biophysica Acta, 2016, 1858(2): 189–196

    Article  CAS  PubMed  Google Scholar 

  45. Ritz S, Schöttler S, Kotman N, Baier G, Musyanovych A, Kuharev J, Landfester K, Schild H, Jahn O, Tenzer S, et al. Protein corona of nanoparticles: Distinct proteins regulate the cellular uptake. Biomacromolecules, 2015, 16(4): 1311–1321

    Article  CAS  PubMed  Google Scholar 

  46. Lundqvist M, Stigler J, Elia G, Lynch I, Cedervall T, Dawson K A. Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts. Proceedings of the National Academy of Sciences of the United States of America, 2008, 105(38): 14265–14270

    Article  PubMed  PubMed Central  Google Scholar 

  47. Townson J L, Lin Y S, Agola J O, Carnes E C, Leong H S, Lewis J D, Haynes C L, Brinker C J. Differing in vivo characteristics of sizeand charge-matched mesoporous silica nanoparticles. Journal of the American Chemical Society, 2013, 135(43): 16030–16033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Röcker C, Pötzl M, Zhang F, Parak W J, Nienhaus G U. A quantitative fluorescence study of protein monolayer formation on colloidal nanoparticles. Nature Nanotechnology, 2009, 4(9): 577–580

    Article  CAS  PubMed  Google Scholar 

  49. Deng Z J, Mortimer G, Schiller T, Musumeci A, Martin D, Minchin R F. Differential plasma protein binding to metal oxide nanoparticles. Nanotechnology, 2009, 20(45): 455101

    Article  CAS  PubMed  Google Scholar 

  50. Lesniak A, Campbell A, Monopoli M P, Lynch I, Salvati A, Dawson K A. Serum heat inactivation affects protein corona composition and nanoparticle uptake. Biomaterials, 2010, 31(36): 9511–5918

    Article  CAS  Google Scholar 

  51. Lesniak A, Fenaroli F, Monopoli M P, Åberg C, Dawson K A, Salvati A. Effects of the presence or absence of a protein corona on silica nanoparticle uptake and impact on cells. ACS Nano, 2012, 6 (7): 5845–5857

    Article  CAS  PubMed  Google Scholar 

  52. Lesniak A, Salvati A, Santos-Martinez M J, Radomski M W, Dawson K A, Åberg C. Nanoparticle adhesion to the cell membrane and its effect on nanoparticle uptake efficiency. Journal of the American Chemical Society, 2013, 135(4): 1438–1444

    Article  CAS  PubMed  Google Scholar 

  53. Murdock R C, Braydich-Stolle L, Schrand A M, Schlager J J, Hussain S M. Characterization of nanomaterial dispersion in solution prior to in vitro exposure using dynamic light scattering technique. Toxicological Sciences: An Official Journal of the Society of Toxicology, 2008, 101(2): 239–253

    Article  CAS  Google Scholar 

  54. Maiorano G, Sabella S, Sorce B, Brunetti V, Malvindi M A, Cingolani R, Pompa P P. Effects of cell culture media on the dynamic formation of protein-nanoparticle complexes and influence on the cellular response. ACS Nano, 2010, 4(12): 7481–7491

    Article  CAS  PubMed  Google Scholar 

  55. Wang J, Jensen U B, Jensen G V, Shipovskov S, Balakrishnan V S, Otzen D, Pedersen J S, Besenbacher F, Sutherland D S. Soft interactions at nanoparticles alter protein function and conformation in a size dependent manner. Nano Letters, 2011, 11(11): 4985–4991

    Article  CAS  PubMed  Google Scholar 

  56. Zhou Y, Fang X, Gong Y, Xiao A, Xie Y, Liu L, Cao Y. The interactions between ZnO nanoparticles (NPs) and α-linolenic acid (LNA) complexed to BSA did not influence the toxicity of ZnO NPs on HepG2 cells. Journal of the American Chemical Society, 2017, 135(4): 1438–1444

    Google Scholar 

  57. Go M R, Yu J, Bae S H, Kim H J, Choi S J. Effects of interactions between ZnO nanoparticles and saccharides on biological responses. International Journal of Molecular Sciences, 2018, 19(2): 486

    Article  CAS  PubMed Central  Google Scholar 

Download references

Acknowledgements

This research was supported by a National Research Foundation of Korea (NRF) awarded by the Korean government (NRF- 2017R1A2B4012636).

Author information

Author notes

  1. These authors contributed equally to this work

Authors and Affiliations

  1. Department of Bionanotechnology and Gachon Medical Research Institute, Gachon University and Gachon Medical Research Institute, Seongnam, Korea

    Vo-Van Giau, Kyu-Hwan Shim & Seong-Soo A. An

  2. Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology and Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, Korea

    Yoon-Hee Park & Sang-Wook Son

Authors
  1. Vo-Van Giau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoon-Hee Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kyu-Hwan Shim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sang-Wook Son
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Seong-Soo A. An
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Sang-Wook Son or Seong-Soo A. An.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Giau, VV., Park, YH., Shim, KH. et al. Dynamic changes of protein corona compositions on the surface of zinc oxide nanoparticle in cell culture media. Front. Chem. Sci. Eng. 13, 90–97 (2019). https://doi.org/10.1007/s11705-018-1766-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11705-018-1766-z

Keywords

Search

Navigation