Platinum nanoparticles (PtNPs) attract much attention due to their excellent biocompatibility and catalytic properties, but their toxic effects on normal (CHANG) and cancerous (HuH-7) human liver cells are meagre. The cytotoxic and apoptotic effects of PtNPs (average size, 3 nm) were determined in CHANG and HuH-7 cells. After treating these cells were with PtNPs (10, 50, 100, 200, and 300 μg/mL) for 24 and 48 hours, we observed dose- and time-dependent cytotoxicity, as evaluated by using (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide, a tetrazole) (MTT) and neutral red uptake (NRU) assays. The production of reactive oxygen species (ROS) was increased in both cells after treatment with the above dose of PtNPs for 24 and 48 hours. Determination of morphological changes of cells, chromosome condensation, mitochondrial membrane potential, and caspase-3 assays showed that PtNPs induce cytotoxicity and apoptosis in CHANG and HuH-7 cells by altering the cell morphology and density, increasing cell population in apoptosis, and causing chromosome condensation. Furthermore, we have studied fragmentation of DNA using alkaline single cell gel electrophoresis and expression of apoptotic genes by real-time PCR (RT-PCR). The percentage of DNA fragmentation was more at 300 μg/mL for 48 hours in both cells, but slightly more fragmentation was found in HuH-7 relative to CHANG cells. Considering all of the above parameters, PtNPs elicited cytotoxicity on CHANG and HuH-7 cells by blocking cell proliferation and inducing apoptosis. Thus this study may be useful in in vitro laboratory studies using cell lines for screening the genotoxic and apoptotic potential of nanoparticles.

中文翻译：

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铂纳米颗粒通过氧化应激介导的 Bax/Bcl-2 和 caspase-3 表达诱导人类正常和癌细胞肝细胞的基因毒性和凋亡活性

铂纳米粒子（PtNPs）因其优异的生物相容性和催化性能而备受关注，但它们对正常（CHANG）和癌性（HuH-7）人肝细胞的毒性作用微乎其微。在 CHANG 和 HuH-7 细胞中测定了 PtNPs（平均大小，3 nm）的细胞毒性和凋亡作用。在用 PtNPs（10、50、100、200 和 300 μg/mL）处理这些细胞 24 和 48 小时后，我们观察到了剂量和时间依赖性细胞毒性，如使用（3-[4, 5-二甲基噻唑-2-基]-2、5-二苯基溴化四唑、四唑) (MTT) 和中性红吸收 (NRU) 测定。在用上述剂量的 PtNPs 处理 24 和 48 小时后，两种细胞中活性氧 (ROS) 的产生均增加。测定细胞形态变化、染色体浓缩、线粒体膜电位和 caspase-3 分析表明，PtNPs 通过改变细胞形态和密度、增加细胞凋亡数量和引起染色体浓缩来诱导 CHANG 和 HuH-7 细胞的细胞毒性和凋亡。此外，我们研究了使用碱性单细胞凝胶电泳的 DNA 片段化和实时 PCR (RT-PCR) 的凋亡基因表达。在 300 μg/mL 时，两种细胞中 DNA 断裂的百分比更高，持续 48 小时，但相对于 CHANG 细胞，HuH-7 中的断裂百分比略高。考虑到上述所有参数，PtNPs 通过阻断细胞增殖和诱导细胞凋亡引起对 CHANG 和 HuH-7 细胞的细胞毒性。