Advertisement

Archives of Toxicology

, Volume 85, Issue 7, pp 799–812 | Cite as

Platinum nanoparticles and their cellular uptake and DNA platination at non-cytotoxic concentrations

  • Helge Gehrke
  • Joanna Pelka
  • Christian G. Hartinger
  • Holger Blank
  • Felix Bleimund
  • Reinhard Schneider
  • Dagmar Gerthsen
  • Stefan Bräse
  • Marlene Crone
  • Michael Türk
  • Doris MarkoEmail author
Inorganic Compounds

Abstract

Three differently sized, highly dispersed platinum nanoparticle (Pt-NP) preparations were generated by supercritical fluid reactive deposition (SFRD) and deposited on a β-cyclodextrin matrix. The average particle size and size distribution were steered by the precursor reduction conditions, resulting in particle preparations of <20, <100 and >100 nm as characterised by TEM and SEM. As reported previously, these Pt-NPs were found to cause DNA strand breaks in human colon carcinoma cells (HT29) in a concentration- and time-dependent manner and a distinct size dependency. Here, we addressed the question whether Pt-NPs might affect directly DNA integrity in these cells and thus behave analogous to platinum-based chemotherapeutics such as cisplatin. Therefore, DNA-associated Pt as well as the translocation of Pt-NPs through a Caco-2 monolayer was quantified by ICP-MS. STEM imaging demonstrated that Pt-NPs were taken up into HT29 cells in their particulate and aggregated form, but appear not to translocate into the nucleus or interact with mitochondria. The platinum content of the DNA of HT29 cells was found to increase in a time- and concentration-dependent manner with a maximal effect at 1,000 ng/cm2. ICP-MS analysis of the cell culture medium indicated the formation of soluble Pt species, although to a limited extent. The observations suggest that DNA strand breaks mediated by metallic Pt-NPs are caused by Pt ions forming during the incubation of cells with these nanoparticles.

Keywords

Cellular localisation Cytotoxicity DNA complexes NP translocation 

Abbreviations

BF

Bright field

Caco-2

Human colon carcinoma cell line

Cisplatin

Cis-diaminedichloridoplatinum

DMEM

Dulbecco’s modified Eagle medium

FCS

Foetal calf serum

GIT

Gastrointestinal tract

HBSS

Hanks’ balanced salt solution

HT29

Human colon carcinoma cell line

ICP-MS

Inductively coupled plasma mass spectrometry

INT

2-(4-Iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium

LDH

Lactate dehydrogenase

LOD

Limit of detection

LOQ

Limit of quantification

PSD

Particle size distribution

Pt

Platinum

PBS

Phosphate-buffered saline

Pt(COD)Me2

1,5-(cyclooctadiene)dimethylplatinum(II)

Pt-NP

Platinum nanoparticle

P/S

Penicillin/streptomycin

ROS

Reactive oxygen species

sc-CO2

Supercritical carbon dioxide

SFRD

Supercritical fluid reactive deposition

SOD

Superoxide dismutase

SOP

Standard operating procedure

SRB

Sulforhodamine B

STEM

Scanning transmission electron microscopy

TEM

Transmission electron microscopy

WST

Water-soluble tetrazolium salt

Notes

Acknowledgments

This work has been partly performed within the project E1.1 of the DFG Research Center for Functional Nanostructures (CFN). It has been further supported by a grant from the Ministry of Science, Research and the Arts of Baden-Württemberg (Az: 7713.14-300).

References

  1. Alt F, Eschnauer HR, Mergler B, Messerschmidt J, Tölg G (1997) A contribution to the ecology and enology of platinum. Fresenius J Anal Chem 357:1013–1019. doi: 10.1007/s002160050296 CrossRefGoogle Scholar
  2. Artelt S, Creutzenberg O, Kock H, Levsen K, Nachtigall D, Heinrich U, Rühle T, Schlögl R (1999) Bioavailability of fine dispersed platinum as emitted from automotive catalytic converters: a model study. Sci Total Environ 228:219–242. doi: 10.1016/S0048-9697(99)00049-2 PubMedCrossRefGoogle Scholar
  3. Asharani PV, Xinyi Ng, Prakash Hande M, Valiyaveettil S (2010) DNA damage and p53-mediated growth arrest in human cells treated with platinum nanoparticles. Nanomedicine 5(1):51–64. doi: 10.2217/nnm.09.85 PubMedCrossRefGoogle Scholar
  4. Borm PJA, Robbins D, Haubold S, Kuhlbush T, Fissan H, Donaldson K, Schins R, Stone V, Kreyling W, Kademann J, Krutmann J, Warheit D, Oberdörster E (2006) The potential risks of nanomaterials: a review carried out for ECETOC. Part Fibre Toxicol 3:11. doi: 10.1186/1743-8977-3-11 PubMedCrossRefGoogle Scholar
  5. Ciccarelli RB, Solomon MJ, Varshavsky A, Lippard SJ (1985) In vivo effects of cis- and trans-diamminedichloroplatinum(II) on SV40 chromosomes: differential repair, DNA-protein cross-linking and inhibition of replication. Biochemistry 24:7533–7540. doi: 10.1021/bi00347a005 PubMedCrossRefGoogle Scholar
  6. Columbo C, Monhemius JA, Plant JA (2008a) The estimation of the bioavailabilities of platinum, palladium and rhodium in vehicle exhaust catalysts and road dusts using a physiologically based extraction test. Sci Total Environ 389:46–51. doi: 10.1016/j.scitotenv.2007.08.002 CrossRefGoogle Scholar
  7. Columbo C, Monhemius JA, Plant JA (2008b) Platinum, palladium and rhodium release from vehicle exhaust catalysts and road dust exposed to simulated lung fluids. Ecotox Environ Safe 71:722–730. doi: 10.1016/j.ecoenv.2007.11.011 CrossRefGoogle Scholar
  8. Donaldson K, Tran L, Jimenez LA, Duffin R, Newby DE, Mills N, MacNee W, Stone V (2005) Combustion-derived nanoparticles: a review of their toxicology following inhalation exposure. Part Fibre Toxicol 2:10. doi: 10.1186/1743-8977-2-10 PubMedCrossRefGoogle Scholar
  9. Elder A, Yang H, Gwiazda R, Teng X, Thurston S, He H, Oberdörster G (2007) Testing nanomaterials of unknown toxicity: an example based on platinum nanoparticles of different shapes. Adv Mater 19:3124–3129. doi: 10.100./adma.200701962 CrossRefGoogle Scholar
  10. Grès M, Julian B, Bourriè M, Meunier V, Roques C, Berger M, Baulence X, Berger Y, Fabre G (1998) Correlation between oral drug absorption in humans and apparent drug permeability in TC-7 cells, a human epithelial intestinal cell line: comparison with the parental Caco-2 cell line. Pharmaceut Res 15:726–733CrossRefGoogle Scholar
  11. Hoppstock K (2001) Platingruppenelemente in der Umwelt. Nachr Chem Tech 49(11):1305–1309. doi: 10.1002/nadc.20010491111 CrossRefGoogle Scholar
  12. Hoppstock K, Alt F (1999) Voltametrische Bestimmung von Platin und Rhodium in Umweltkompartimenten und biologischen Materialien. In: Zereini F, Alt F (eds) Emissionen von Platinmetallen. Springer, Berlin, Heidelberg, pp 230–257Google Scholar
  13. Jordan P, Carmo-Fonseca M (2000) Molecular mechanisms involved in cisplatin cytotoxicity. Cell Mol Life Sci 57:1229–1235. doi: 10.1007/PL00000762 PubMedCrossRefGoogle Scholar
  14. Kajita M, Hikosaka K, Litsuka M, Kanayama A, Toshima N, Miyamoto Y (2007) Platinum nanoparticle is a useful scavenger of superoxide anion and hydrogen peroxide. Free Radic Res 41(6):615–626. doi: 10.1080/10715760601169679 PubMedCrossRefGoogle Scholar
  15. López T, Figueras F, Manjarrez J, Bustos J, Alvarez M, Silvestre-Albero J, Rodríguez-Reinoso F, Martínez-Ferre A, Martínez E (2010) Catalytic nanomedicine: a new field in antitumor treatment using supported platinum nanoparticles. In vitro DNA degradation and in vivo test with C6 animal model on Wistar rats. Eur J Med Chem 45(5):1982–1990. doi: 10.1016/j.ejmech.2010.01.043 Google Scholar
  16. Oberdörster G, Oberdörster E, Oberdörster J (2005) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113:823–839. doi: 10.1289/ehp.7339 PubMedCrossRefGoogle Scholar
  17. Pelka J, Gehrke H, Esselen M, Türk M, Crone M, Bräse S, Muller T, Blank H, Send W, Zibat V, Brenner P, Schneider R, Gerthsen D, Marko D (2009) Cellular uptake of platinum nanoparticles in human colon carcinoma cells and their impact on cellular redox systems and DNA integrity. Chem Res Tox 22:649–659. doi: 10.1021/tx800354g CrossRefGoogle Scholar
  18. Porcel E, Liehn S, Remita H, Usami N, Kobayashi K, Furusawa Y, Le Sech C, Lacombe S (2010) Platinum nanoparticles: a promising material for future cancer therapy? Nanotechnology 21(8):085103. doi: 10.1088/0957-4484/21/8/085103
  19. Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, Warren JT, Bokesch H, Kenney S, Boyd MR (1990) New colorimetric assay for anticancer-drug screening. J Natl Cancer Inst 82:1107–1112. doi: 10.1093/jnci/82.13.1107 PubMedCrossRefGoogle Scholar
  20. Watanabe A, Kajita M, Kim J, Kanayama A, Takahashi K, Mashino T, Miyamoto Y (2009) In vitro free radical scavenging activity of platinum nanoparticles. Nanotechnology 20:455105PubMedCrossRefGoogle Scholar
  21. Zample DB, Lippard SJ (1995) Cisplatin and DNA repair in cancer chemotherapy. Trends Biochem Sci 20:435–439. doi: 10.1016/S0968-0004(00)89095-7 CrossRefGoogle Scholar
  22. Zereini F, Alt F, Messerschmidt J, von Bohlen A, Liebl K, Puttmann W (2004) Concentration and distribution of platinum group elements (Pt, Pd, Rh) in airborne particulate matter in Frankfurt am Main, Germany. Environ Sci Technol 38:1686–1692PubMedCrossRefGoogle Scholar
  23. Zereini F, Wiseman C, Puttmann W (2007) Changes in palladium, platinum, and rhodium concentrations, and their spatial distribution in soils along a major highway in Germany from 1994 to 2004. Environ Sci Technol 41:451–456PubMedCrossRefGoogle Scholar
  24. Zhong CJ, Maye MM, Luo J, Kariuki N (2004) Nanoparticles in catalysis. In: Rotello V (ed) Nanoparticles: building blocks for nanotechnology. Kluwer Academics, Plenum Publishers, New York, pp 113–140Google Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Helge Gehrke
    • 1
  • Joanna Pelka
    • 1
  • Christian G. Hartinger
    • 2
  • Holger Blank
    • 3
  • Felix Bleimund
    • 3
  • Reinhard Schneider
    • 3
  • Dagmar Gerthsen
    • 3
  • Stefan Bräse
    • 4
  • Marlene Crone
    • 5
  • Michael Türk
    • 5
  • Doris Marko
    • 1
    Email author
  1. 1.Department of Food Chemistry and ToxicologyUniversity of ViennaViennaAustria
  2. 2.Institute of Inorganic ChemistryUniversity of ViennaViennaAustria
  3. 3.Laboratorium für ElektronenmikroskopieKarlsruher Institut für TechnologieKarlsruheGermany
  4. 4.Karlsruher Institut für TechnologieInstitut für Organische ChemieKarlsruheGermany
  5. 5.Karlsruher Institut für TechnologieInstitut für Technische Thermodynamik und KältetechnikKarlsruheGermany

Personalised recommendations