Advertisement

Journal of Nanoparticle Research

, Volume 13, Issue 7, pp 3019–3032 | Cite as

Zinc-phosphate nanoparticles with reversibly attached TNF-α analogs: an interesting concept for potential use in active immunotherapy

  • Gorazd Hribar
  • Andrej Žnidaršič
  • Marjan Bele
  • Uroš Maver
  • Simon Caserman
  • Miran Gaberšček
  • Vladka Gaberc-Porekar
Research paper

Abstract

The authors’ intention was to prepare nanometer-sized zinc-phosphate nanoparticles that would be capable of binding histidine-rich TNF-α analogs onto their surface via a coordinative bond. Zinc-phosphate nanoparticles with a size of around 60 nm were prepared by a wet precipitation method and characterized using SEM, EDX, XRD, and DLS. First, BSA was bound as a testing protein, afterward two TNF-α analogs with decreased activity were bound to the described nanoparticles. The efficiency of binding and the existence of coordinative bond were confirmed with SDS-PAGE analysis. During binding, particle storage, and release experiments, the prepared TNF-α analogs retained their biological activity—hence the epitopes necessary for formation of antibodies stayed intact. The particle size did not change within a period of 2 weeks. No significant agglomeration was observed, the particles could be quickly dispersed in ultrasound. The present nanoparticles and the general approach of coordinative binding are widely applicable for natural and engineered histidine-rich proteins. The nanoparticles bearing appropriate TNF-α analogs could also be potentially used for active immunotherapy to tackle the chronic inflammatory diseases associated with pathogenically elevated levels of TNF-α.

Keywords

TNF-α analog Protein nanoparticle Zinc-phosphate Chronic inflammatory disease Coordinative binding Histidine residue Nanomedicine 

Notes

Acknowledgments

This manuscript is dedicated to the memory of Dr. Viktor Menart, who was the initiator and the scientific leader of this study. The study has been financially supported by the Slovenian Research Agency and by the European Commission under the Sixth Framework Program.

References

  1. Augustsson J, Jonsdottir T, Klareskog L, van Vollenhoven RF (2006) Infliximab in the treatment of rheumatoid arthritis. Aging Health 2(1):19–33CrossRefGoogle Scholar
  2. Bele M, Hribar G, Campelj S et al (2008) Zinc-decorated silica-coated magnetic nanoparticles for protein binding and controlled release. J Chromatogr B 867(1):160–164CrossRefGoogle Scholar
  3. Boehncke WH (2007) Etanercept: a soluble TNF-α receptor in the treatment of psoriasis. Therapy 4(5):665–672CrossRefGoogle Scholar
  4. Chaga GS (2001) Twenty-five years of immobilized metal ion affinity chromatography: past, present and future. J Biochem Biophys Methods 49(1–3):313–334CrossRefGoogle Scholar
  5. Chikh GG, Li WM, Schutze-Redelmeier MP, Meunier JC, Bally MB (2002) Attaching histidine-tagged peptides and proteins to lipid-based carriers through use of metal-ion-chelating lipids. Biochim Biophys Acta 1567(1–2):204–212Google Scholar
  6. Dalum I, Butler DM, Jensen MR et al (1999) Therapeutic antibodies elicited by immunization against TNF-alpha. Nat Biotechnol 17(7):666–669CrossRefGoogle Scholar
  7. Delavallee L, Assier E, Denys A, Falgarone G, Zagury JF, Muller S, Bessis N, Boissier MC (2008) Vaccination with cytokines in autoimmune diseases. Ann Med 40(5):343–351CrossRefGoogle Scholar
  8. Fonda I, Kenig M, Gaberc-Porekar V, Pristovsek P, Menart V (2002) Attachment of histidine tags to recombinant tumor necrosis factor-alpha drastically changes its properties. Sci World J 2:1312–1325Google Scholar
  9. Frenzel A, Bergemann C, Kohl G, Reinard T (2003) Novel purification system for 6xHis-tagged proteins by magnetic affinity separation. J Chromatogr B 793(2):325–329CrossRefGoogle Scholar
  10. Gaberc-Porekar V, Menart V (2001) Perspectives of immobilized-metal affinity chromatography. J Biochem Biophys Methods 49(1–3):335–360CrossRefGoogle Scholar
  11. Gaberc-Porekar V, Menart V (2005) Potential for using histidine tags in purification of proteins at large scale. Chem Eng Technol 28(11):1306–1314CrossRefGoogle Scholar
  12. Gaberc-Porekar V, Menart V, Jevsevar S, Vidensek A, Stalc A (1999) Histidines in affinity tags and surface clusters for immobilized metal-ion affinity chromatography of trimeric tumor necrosis factor alpha. J Chromatogr A 852(1):117–128CrossRefGoogle Scholar
  13. Herschke L, Lieberwirth I, Wegner G (2006a) Zinc phosphate as versatile material for potential biomedical applications Part II. J Mater Sci 17(1):95–104Google Scholar
  14. Herschke L, Rottstegge J, Lieberwirth I, Wegner G (2006b) Zinc phosphate as versatile material for potential biomedical applications part 1. J Mater Sci 17(1):81–94Google Scholar
  15. Hillaireau H, Couvreur P (2009) Nanocarriers’ entry into the cell: relevance to drug delivery. Cell Mol Life Sci 66(17):2873–2896CrossRefGoogle Scholar
  16. Holtmann MH, Neurath MF (2004) Differential TNF-signaling in chronic inflammatory disorders. Curr Mol Med 4(4):439–444CrossRefGoogle Scholar
  17. Lee SJ, Kavanaugh A (2005) Adalimumab for the treatment of rheumatoid arthritis. Therapy 2(1):13–21CrossRefGoogle Scholar
  18. Mease JP (2009) Certolizumab pegol for rheumatoid arthritis: effective in combination with methotrexate or as monotherapy. Int J Clin Rheumatol 4(3):253–266CrossRefGoogle Scholar
  19. Patel JD, O’Carra R, Jones J, Woodward JG, Mumper RJ (2007) Preparation and characterization of nickel nanoparticles for binding to his-tag proteins and antigens. Pharm Res 24(2):343–352CrossRefGoogle Scholar
  20. Spohn G, Guler R, Johansen P et al (2007) A virus-like particle-based vaccine selectively targeting soluble TNF-alpha protects from arthritis without inducing reactivation of latent tuberculosis. J Immunol 178(11):7450–7457Google Scholar
  21. Sprules T, Green N, Featherstone M, Gehring K (1998) Nickel-induced oligomerization of proteins containing 10-histidine tags. Biotechniques 25(1):20–22Google Scholar
  22. Steed PM, Tansey MG, Zalevsky J, Zhukovsky EA, Desjarlais JR, Szymkowski DE, Abbott C, Carmichael D, Chan C, Cherry L et al (2003) Inactivation of TNF signaling by rationally designed dominant-negative TNF variants. Science 301(5641):1895–1898CrossRefGoogle Scholar
  23. Tabata Y, Noda Y, Matsui Y, Ikada Y (1999) Targeting of tumor necrosis factor to tumor by use of dextran and metal coordination. J Control Release 59(2):187–196CrossRefGoogle Scholar
  24. Tian ZM, Wan MX, Wang B, Wang SP, Wu XM, Ruan YS (2003) Effects of ultrasound on the structure and function of tumor necrosis factor-alpha. Ultrasound Med Biol 29(9):1331–1339CrossRefGoogle Scholar
  25. Wajant H, Pfizenmaier K, Scheurich P (2003) Tumor necrosis factor signaling. Cell Death Differ 10(1):45–65CrossRefGoogle Scholar
  26. Wang TW, Xu Q, Wu Y, Zeng AJ, Li MJ, Gao HX (2009) Quaternized chitosan (QCS)/poly (aspartic acid) nanoparticles as a protein drug-delivery system. Carbohydr Res 344(7):908–914CrossRefGoogle Scholar
  27. Watanabe M, Uchida K, Nakagaki K et al (2007) Anti-cytokine autoantibodies are ubiquitous in healthy individuals. FEBS Lett 581(10):2017–2021CrossRefGoogle Scholar
  28. Zuany-Amorim C, Manlius C, Dalum I et al (2004) Induction of TNF-alpha autoantibody production by AutoVac TNF106: a novel therapeutic approach for the treatment of allergic diseases. Int Arch Allergy Immunol 133(2):154–163CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Gorazd Hribar
    • 1
  • Andrej Žnidaršič
    • 2
  • Marjan Bele
    • 2
  • Uroš Maver
    • 2
  • Simon Caserman
    • 1
  • Miran Gaberšček
    • 2
  • Vladka Gaberc-Porekar
    • 1
  1. 1.Laboratory for Biosynthesis and BiotransformationNational Institute of ChemistryLjubljanaSlovenia
  2. 2.Laboratory for Materials ElectrochemistryNational Institute of ChemistryLjubljanaSlovenia

Personalised recommendations