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.

Effects triggered by platinum nanoparticles on primary keratinocytes

“…However, such DNA damage was not accompanied by the formation of ROS. 23,24 In this study, we used PtNPs coated with PVP, which represent a polymer increasingly widespread in medicine and foodstuffs. First of all, PVP is used as a binder in many pharmaceutical tablets.…”

Cytotoxic and Antiproliferative Effects of Nanomaterials on Cancer Cell Lines: A Review

“…PtNPs released Pt ions that may bind to DNA leading to strand cleavage damage [49]. Another important feature is the synergistic antitumor activity between platinum and gold NPs.…”

The formation of intracellular nanoparticles correlates with cisplatin resistance

“…In contrast, the cytotoxicity of Pt-NPs is quite limited [34][35][36][37][38][39][40]. Therefore, the conversion of internalized cisplatin molecules into Pt-NPs within cells might have contributed to the apparent drug resistance with tumor cells, which often express high levels of antioxidant enzymes such as GST [22][23][24].…”