caa a22 4500 445853018 CHVBK 20180317145419.0 cr unu---uuuuu 170323e20110701xx s 000 0 eng 10.1007/s00204-010-0636-3 doi (NATIONALLICENCE)springer-10.1007/s00204-010-0636-3 Platinum nanoparticles and their cellular uptake and DNA platination at non-cytotoxic concentrations [Elektronische Daten] [Helge Gehrke, Joanna Pelka, Christian Hartinger, Holger Blank, Felix Bleimund, Reinhard Schneider, Dagmar Gerthsen, Stefan Bräse, Marlene Crone, Michael Türk, Doris Marko] 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 >100nm 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 1,000ng/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. Springer-Verlag, 2011 Cellular localisation nationallicence Cytotoxicity nationallicence DNA complexes nationallicence NP translocation nationallicence BF : Bright field nationallicence Caco-2 : Human colon carcinoma cell line nationallicence Cisplatin : Cis-diaminedichloridoplatinum nationallicence DMEM : Dulbecco's modified Eagle medium nationallicence FCS : Foetal calf serum nationallicence GIT : Gastrointestinal tract nationallicence HBSS : Hanks' balanced salt solution nationallicence HT29 : Human colon carcinoma cell line nationallicence ICP-MS : Inductively coupled plasma mass spectrometry nationallicence INT : 2-(4-Iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium nationallicence LDH : Lactate dehydrogenase nationallicence LOD : Limit of detection nationallicence LOQ : Limit of quantification nationallicence PSD : Particle size distribution nationallicence Pt : Platinum nationallicence PBS : Phosphate-buffered saline nationallicence Pt(COD)Me2 : 1,5-(cyclooctadiene)dimethylplatinum(II) nationallicence Pt-NP : Platinum nanoparticle nationallicence P/S : Penicillin/streptomycin nationallicence ROS : Reactive oxygen species nationallicence sc-CO2 : Supercritical carbon dioxide nationallicence SFRD : Supercritical fluid reactive deposition nationallicence SOD : Superoxide dismutase nationallicence SOP : Standard operating procedure nationallicence SRB : Sulforhodamine B nationallicence STEM : Scanning transmission electron microscopy nationallicence TEM : Transmission electron microscopy nationallicence WST : Water-soluble tetrazolium salt nationallicence Gehrke Helge Department of Food Chemistry and Toxicology, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria aut Pelka Joanna Department of Food Chemistry and Toxicology, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria aut Hartinger Christian Institute of Inorganic Chemistry, University of Vienna, Währinger Straße 42, 1090, Vienna, Austria aut Blank Holger Laboratorium für Elektronenmikroskopie, Karlsruher Institut für Technologie, Engesserstrasse 7, 76131, Karlsruhe, Germany aut Bleimund Felix Laboratorium für Elektronenmikroskopie, Karlsruher Institut für Technologie, Engesserstrasse 7, 76131, Karlsruhe, Germany aut Schneider Reinhard Laboratorium für Elektronenmikroskopie, Karlsruher Institut für Technologie, Engesserstrasse 7, 76131, Karlsruhe, Germany aut Gerthsen Dagmar Laboratorium für Elektronenmikroskopie, Karlsruher Institut für Technologie, Engesserstrasse 7, 76131, Karlsruhe, Germany aut Bräse Stefan Karlsruher Institut für Technologie, Institut für Organische Chemie, Fritz-Haber-Weg 6, 76131, Karlsruhe, Germany aut Crone Marlene Karlsruher Institut für Technologie, Institut für Technische Thermodynamik und Kältetechnik, Engler-Bunte-Ring 21, 76131, Karlsruhe, Germany aut Türk Michael Karlsruher Institut für Technologie, Institut für Technische Thermodynamik und Kältetechnik, Engler-Bunte-Ring 21, 76131, Karlsruhe, Germany aut Marko Doris Department of Food Chemistry and Toxicology, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria aut Archives of Toxicology Springer-Verlag 85/7(2011-07-01), 799-812 0340-5761 85:7<799 2011 85 204 https://doi.org/10.1007/s00204-010-0636-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-010-0636-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gehrke Helge Department of Food Chemistry and Toxicology, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria aut NATIONALLICENCE 700 1- Pelka Joanna Department of Food Chemistry and Toxicology, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria aut NATIONALLICENCE 700 1- Hartinger Christian Institute of Inorganic Chemistry, University of Vienna, Währinger Straße 42, 1090, Vienna, Austria aut NATIONALLICENCE 700 1- Blank Holger Laboratorium für Elektronenmikroskopie, Karlsruher Institut für Technologie, Engesserstrasse 7, 76131, Karlsruhe, Germany aut NATIONALLICENCE 700 1- Bleimund Felix Laboratorium für Elektronenmikroskopie, Karlsruher Institut für Technologie, Engesserstrasse 7, 76131, Karlsruhe, Germany aut NATIONALLICENCE 700 1- Schneider Reinhard Laboratorium für Elektronenmikroskopie, Karlsruher Institut für Technologie, Engesserstrasse 7, 76131, Karlsruhe, Germany aut NATIONALLICENCE 700 1- Gerthsen Dagmar Laboratorium für Elektronenmikroskopie, Karlsruher Institut für Technologie, Engesserstrasse 7, 76131, Karlsruhe, Germany aut NATIONALLICENCE 700 1- Bräse Stefan Karlsruher Institut für Technologie, Institut für Organische Chemie, Fritz-Haber-Weg 6, 76131, Karlsruhe, Germany aut NATIONALLICENCE 700 1- Crone Marlene Karlsruher Institut für Technologie, Institut für Technische Thermodynamik und Kältetechnik, Engler-Bunte-Ring 21, 76131, Karlsruhe, Germany aut NATIONALLICENCE 700 1- Türk Michael Karlsruher Institut für Technologie, Institut für Technische Thermodynamik und Kältetechnik, Engler-Bunte-Ring 21, 76131, Karlsruhe, Germany aut NATIONALLICENCE 700 1- Marko Doris Department of Food Chemistry and Toxicology, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/7(2011-07-01), 799-812 0340-5761 85:7<799 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer