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

  • Inorganic Compounds
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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.

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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

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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).

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Authors and Affiliations

  1. Department of Food Chemistry and Toxicology, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria

    Helge Gehrke, Joanna Pelka & Doris Marko

  2. Institute of Inorganic Chemistry, University of Vienna, Währinger Straße 42, 1090, Vienna, Austria

    Christian G. Hartinger

  3. Laboratorium für Elektronenmikroskopie, Karlsruher Institut für Technologie, Engesserstrasse 7, 76131, Karlsruhe, Germany

    Holger Blank, Felix Bleimund, Reinhard Schneider & Dagmar Gerthsen

  4. Karlsruher Institut für Technologie, Institut für Organische Chemie, Fritz-Haber-Weg 6, 76131, Karlsruhe, Germany

    Stefan Bräse

  5. Karlsruher Institut für Technologie, Institut für Technische Thermodynamik und Kältetechnik, Engler-Bunte-Ring 21, 76131, Karlsruhe, Germany

    Marlene Crone & Michael Türk

Authors
  1. Helge Gehrke
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  2. Joanna Pelka
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Correspondence to Doris Marko.

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Gehrke, H., Pelka, J., Hartinger, C.G. et al. Platinum nanoparticles and their cellular uptake and DNA platination at non-cytotoxic concentrations. Arch Toxicol 85, 799–812 (2011). https://doi.org/10.1007/s00204-010-0636-3

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  • DOI: https://doi.org/10.1007/s00204-010-0636-3

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