Platinum nanoparticles and their cellular uptake and DNA platination at non-cytotoxic concentrations
Platinum nanoparticles and their cellular uptake and DNA platination at non-cytotoxic concentrations
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DOI：
10.1007/s00204-010-0636-3
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发表时间：
2011-07-01
影响因子：
6.1
通讯作者：
Marko, Doris
中科院分区：
文献类型：
--
作者：
Gehrke, Helge;Pelka, Joanna;Marko, Doris
三种不同尺寸的，高度分散的铂纳米颗粒（Pt-NP）制剂产生的超临界流体反应沉积（SFRD）和沉积在β-环糊精基质。通过前体还原条件来控制平均粒度和粒度分布，得到< 100 and >如通过TEM和SEM表征的< 20，100 nm的颗粒制剂。如前所述，发现这些Pt-NP以浓度和时间依赖性方式以及明显的大小依赖性引起人结肠癌细胞（HT 29）中的DNA链断裂。在这里，我们解决了Pt-NPs是否可能直接影响这些细胞中的DNA完整性的问题，从而表现出类似于基于铂的化疗药物，如顺铂。因此，DNA相关的Pt以及Pt-NPs通过Caco-2单层的易位通过ICP-MS进行定量。STEM成像表明Pt-NPs以其颗粒和聚集形式被摄取到HT 29细胞中，但似乎不易位到细胞核中或与线粒体相互作用。发现HT 29细胞DNA中的铂含量以时间和浓度依赖性方式增加，最大效应为1，000 ng/cm（2）。细胞培养基的ICP-MS分析表明形成了可溶性Pt物质，尽管程度有限。观察结果表明，由金属Pt-NP介导的DNA链断裂是由在细胞与这些纳米颗粒孵育期间形成的Pt离子引起的。
Three differently sized, highly dispersed platinum nanoparticle (Pt-NP) preparations were generated by supercritical fluid reactive deposition (SFRD) and deposited on a beta-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.