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In Vivo Testing for Gold Nanoparticle Toxicity

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NanoBiotechnology Protocols

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1026))

Abstract

A technique for measuring the toxicity of nanomaterials using a murine model is described. Blood samples are collected via submandibular bleeding while urine samples are collected on cellophane sheets. Both biosamples are then analyzed by inductively coupled plasma optical emission spectroscopy (ICP-OES) for nanotoxicity. Blood samples are further tested for immunological response using a standard Coulter counter. The major organs of interest for filtration are also digested and analyzed via ICP-OES, producing useful information regarding target specificity of the nanomaterial of interest. Collection of the biosamples and analysis afterward is detailed, and the operation of the technique is described and illustrated by analysis of the nanotoxicity of an injection of a modified tiopronin monolayer-protected cluster.

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References

  1. Cherukuri P, Gannon CJ, Leeuw TK, Schmidt HK, Smalley RE, Curley SA, Weisman RB (2006) Mammalian pharmacokinetics of carbon nanotubes using intrinsic near-infrared fluorescence. Proc Natl Acad Sci USA 103:18882–18886

    Article  CAS  Google Scholar 

  2. Stroh M, Zimmer JP, Duda DG, Levchenko TS, Cohen KS, Brown EB, Scadden DT, Torchilin VP, Bawendi MG, Fukumura D, Jain RK (2005) Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo. Nat Med 11:678–682

    Article  CAS  Google Scholar 

  3. Zimmer JP, Kim S-W, Ohnishi S, Tanaka E, Frangioni JV, Bawendi MG (2006) Size series of small indium arsenide-zinc selenide core-shell nanocrystals and their application to in vivo imaging. J Am Chem Soc 128:2526–2527

    Article  CAS  Google Scholar 

  4. Eck W, Craig G, Sigdel A, Ritter G, Old LJ, Tang L, Brennan MF, Allen PJ, Mason MD (2008) Pegylated gold nanoparticles conjugated to monoclonal F19 antibodies as targeted labeling agents for human pancreatic carcinoma tissue. ACS Nano 2:2263–2272

    Article  CAS  Google Scholar 

  5. Everts M, Saini V, Leddon JL, Kok RJ, Stoff-Khalili M, Preuss MA, Millican CL, Perkins G, Brown JM, Bagaria H, Nikles DE, Johnson DT, Zharov VP, Curiel DT (2006) Covalently linked Au nanoparticles to a viral vector: potential for combined photothermal and gene cancer therapy. Nano Lett 6:587–591

    Article  CAS  Google Scholar 

  6. Tkachenko AG, Xie H, Coleman D, Glomm W, Ryan J, Anderson MF, Franzen S, Feldheim DL (2003) Multifunctional gold nanoparticle-peptide complexes for nuclear targeting. J Am Chem Soc 125:4700–4701

    Article  CAS  Google Scholar 

  7. Hainfeld JF, Slatkin DN, Smilowitz HM (2004) The use of gold nanoparticles to enhance radiotherapy in mice. Phys Med Biol 49:309–315

    Article  Google Scholar 

  8. Hainfeld JF, Slatkin DN, Focella TM, Smilowitz HM (2006) Gold nanoparticles: a new X-ray contrast agent. Br J Radiol 79:248–253

    Article  CAS  Google Scholar 

  9. Khlebtsov B, Zharov V, Melnikov A, Tuchin V, Khlebtsov N (2006) Optical amplification of photothermal therapy with gold nanoparticles and nanoclusters. Nanotechnology 17:5167–5179

    Article  CAS  Google Scholar 

  10. Taubert A, Napoli A, Meier W (2004) Self-assembly of reactive amphiphilic block copolymers as mimetics for biological membranes. Curr Opin Chem Biol 8:598–603

    Article  CAS  Google Scholar 

  11. Ranney DF (2000) Biomimetic transport and rational drug delivery. Biochem Pharmacol 59:105–114

    Article  CAS  Google Scholar 

  12. Choi HS, Liu W, Misra P, Tanaka E, Zimmer JP, Ipe BI, Bawendi MG, Fangioni JV (2007) Renal clearance of quantum dots. Nat Biotechnol 25:1165–1170

    Article  CAS  Google Scholar 

  13. Moghimi SM, Porter CJH, Muir IS, Illum L, Davis SS (1991) Non-phagocytic uptake of intravenously injected microspheres in rat spleen: influence of particle size and hydrophilic coating. Biochem Biophys Res Commun 177:861–866

    Article  CAS  Google Scholar 

  14. De Jong WH, Hagens WI, Krystek P, Burger MC, Sips AJAM, Geertsma RE (2008) Particle size-dependent organ distribution of gold nanoparticles after intravenous administration. Biomaterials 29:1912–1919

    Article  Google Scholar 

  15. Sonavane G, Tomoda K, Sano A, Ohshima H, Terada H, Makino K (2008) In vitro permeation of gold nanoparticles through rat skin and rat intestine: effect of particle size. Colloids Surf B Biointerfaces 65:1–10

    Article  CAS  Google Scholar 

  16. Armstrong JK, Meiselman HJ, Wenby RB, Fisher TC (2003) In vivo survival of poly(ethylene glycol)-coated red blood cells in the rabbit. Blood 102:94A

    Article  Google Scholar 

  17. Gerdon AE, Wright DW, Cliffel DE (2005) Hemagglutinin linear epitope presentation on monolayer-protected clusters elicits strong antibody binding. Biomacromolecules 6:3419–3424

    Article  CAS  Google Scholar 

  18. Gerdon AE, Wright DW, Cliffel DE (2006) Epitope mapping of the protective antigen of B. anthracis by using nanoclusters presenting conformational peptide epitopes. Angew Chem Int Ed Engl 45:594–598

    Article  CAS  Google Scholar 

  19. Owens DE, Peppas NA (2006) Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm 307:93–102

    Article  CAS  Google Scholar 

  20. Alexis F, Pridgen E, Molnar LK, Farokhzad OC (2008) Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm 5:505–515

    Article  CAS  Google Scholar 

  21. Moghimi SM, Hunter AC, Murray JC (2001) Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol Rev 53:283–318

    CAS  Google Scholar 

  22. Richter AW, Akerblom E (1984) Polyethylene glycol reactive antibodies in man: titer distribution in allergic patients treated with monomethoxy polyethylene glycol modified allergens or placebo, a Nd in healthy blood donors. Int Arch Allery Appl Immunol 74:36–39

    Article  CAS  Google Scholar 

  23. Armstrong JK, Hempel G, Koling S, Chan LS, Fisher TC, Meiselman HJ, Garratty G (2007) Antibody against poly(ethylene glycol) adversely affects PEG-asparaginase therapy in acute lymphoblastic leukemia patients. Cancer 110:103–111

    Article  Google Scholar 

  24. Armstrong JK, Leger R, Wenby RB, Meiselman HJ, Garratty G, Fisher TC (2003) Occurrence of an antibody to poly(ethylene glycol) in normal donors. Blood 102:556A

    Google Scholar 

  25. Leger RM, Arndt P, Garratty G, Armstrong JK, Meiselman HJ, Fisher TC (2001) Normal donor sera can contain antibodies to polyethylene glycol (PEG). Transfusion 41:29S

    Google Scholar 

  26. Simpson CA, Huffman BJ, Gerdon AE, Cliffel DE (2010) Unexpected toxicity of monolayer protected gold clusters eliminated by PEG-thiol place-exchange reactions. Chem Res Toxicol 23:1608–1616

    Article  CAS  Google Scholar 

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Simpson, C.A., Huffman, B.J., Cliffel, D.E. (2013). In Vivo Testing for Gold Nanoparticle Toxicity. In: Rosenthal, S., Wright, D. (eds) NanoBiotechnology Protocols. Methods in Molecular Biology, vol 1026. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-468-5_14

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  • DOI: https://doi.org/10.1007/978-1-62703-468-5_14

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-467-8

  • Online ISBN: 978-1-62703-468-5

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