title: Platinum nanoparticles and their cellular uptake and DNA platination at non-cytotoxic concentrations.
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/cm(2). 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.
authors.affiliation: Department of Food Chemistry and Toxicology, University of Vienna, Vienna, Austria.
authors.forename: Helge
authors.initials: H
authors.lastname: Gehrke
authors.forename: Joanna
authors.initials: J
authors.lastname: Pelka
authors.forename: Christian G
authors.initials: CG
authors.lastname: Hartinger
authors.forename: Holger
authors.initials: H
authors.lastname: Blank
authors.forename: Felix
authors.initials: F
authors.lastname: Bleimund
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schneider
authors.forename: Dagmar
authors.initials: D
authors.lastname: Gerthsen
authors.forename: Stefan
authors.initials: S
authors.lastname: Bräse
authors.forename: Marlene
authors.initials: M
authors.lastname: Crone
authors.forename: Michael
authors.initials: M
authors.lastname: Türk
authors.forename: Doris
authors.initials: D
authors.lastname: Marko
mesh_terms: D018938:Caco-2 Cells; D016764:Cell Polarity; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000737:chemistry; D022162:Cytoplasmic Vesicles / Q000737:chemistry / Q000648:ultrastructure; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism*; D020895:Enterocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D019073:HT29 Cells; D006801:Humans; D007408:Intestinal Absorption; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D009153:Mutagens / Q000032:analysis / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D009944:Organoplatinum Compounds; D009994:Osmolar Concentration; D010316:Particle Size; D010984:Platinum / Q000032:analysis / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D012995:Solubility; D013997:Time Factors
chemical_list: D017077:Culture Media, Conditioned; D009153:Mutagens; D009944:Organoplatinum Compounds; D010984:Platinum; D004247:DNA