聚乙二醇包被和未包被金纳米颗粒对人肾(HK-2)细胞的细胞毒性和遗传毒性的物理化学表征和评估

Rogers Cr, D. S, Patlolla Ak, Tchounwou Pb
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摘要

虽然金纳米颗粒(Au-NPs)由于其独特的物理化学性质、化学稳定性和生物相容性已广泛用于医学诊断和治疗患者,但最近的报道也强调了其对人体的毒性。在本研究中,我们研究了未包被和聚乙二醇包被的AuNPs对人肾(HK-2)细胞的毒性作用。两种形式的AuNP均采用标准方案合成和表征。采用动态光散射(DLS)、Zeta Sizer Nano ZS分析仪、透射电子显微镜(TEM)和电感耦合等离子体发射光谱(ICP-OES)分别测量了它们的分布、Zeta电位/表面电荷、形态尺寸和Au浓度。采用细胞毒素法和台盼蓝排除法测定细胞毒性。通过定量测定谷胱甘肽(GSH)和线粒体膜电位(MMP)水平来评估氧化应激(OS)。采用单细胞凝胶电泳(Comet法)和染色体畸变(CA)法评估遗传毒性。未包被的AuNPs显著降低细胞活力,增加ROS,降低GSH,使MMP去极化,并以浓度依赖的方式诱导显著的DNA损伤和染色体改变,包括染色体间隙、中心环、断裂、缺失以及染色体内和染色体间交换。peg包被的AuNPs表现出较低的细胞毒性和遗传毒性作用,并且没有产生任何明显的ROS增加或GSH显著减少,并且MMP的极化可以忽略不计。因此,peg包被的AuNPs比未包被的AuNPs毒性相对较小,因此在纳米医学中可能有潜在的应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Physico-Chemical Characterization and Assessment of Cytotoxic and Genotoxic Effects of Poly-Ethylene-Glycol Coated and Uncoated Gold Nanoparticles on Human Kidney (HK-2) Cells
Although gold Nanoparticles (Au-NPs) have been widely used in medicine for the diagnosis and treatment of patients due to their unique physicochemical properties, chemical stability and biocompatibility, recent reports have also highlighted their potential to induce toxicity to humans. In the present study, we investigated the toxic effects of uncoated and Polyethylene Glycol (PEG)-coated AuNPs on human kidney (HK-2) cells. Both forms of AuNP were synthesized and characterized using standard protocols. Dynamic Light Scattering (DLS), Zeta Sizer Nano ZS analyzer, Transmission Electron Microscopy (TEM), and Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES) were used to measure their distribution, zeta potential/surface charge, morphological size, and Au concentrations, respectively. Cytotoxicity was measured by Cyto- Tox assay and trypan blue exclusion test. Oxidative Stress (OS) was assessed by quantifying the levels of Glutathione (GSH), and Mitochondria Membrane Potential (MMP). Genotoxicity was assessed by single cell gel electrophoresis (Comet assay) and Chromosomal Aberration (CA) assay. Uncoated AuNPs significantly reduced cell viability, increased ROS, decreased GSH, depolarized the MMP, and induced significant DNA damage and chromosomal alterations including chromosome gaps, centric rings, breaks, deletions, and intra and interchromosome exchanges, in a concentration-dependent manner. PEG-coated AuNPs displayed lower cytotoxic and genotoxic effects, and did not produce any significant increase in ROS or significant decrease in GSH along with negligible polarization of the MMP. Hence, PEG-coated AuNPs are relatively less toxic than uncoated AuNPs and therefore, may have potential applications in nanomedicine.
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