NIH-RCMI Center for Environmental Health, College of Science Engineering and Technology, Jackson State University, Jackson, MS, 39217, USA,
Department of Biology, CSET, Jackson State University, Jackson, MS, 39217, USA,
Int J Nanomedicine. 2019 Jan 15;14:639-647. doi: 10.2147/IJN.S185574. eCollection 2019.
Gold nanoparticles (GNPs) and their functional derivatives are of great interest because of their many biomedical applications. GNPs are increasingly being incorporated into new diagnostic and therapeutic approaches in medicine. Consequently, there has been a strong push to fully understand their interactions with blood components. The agglomeration of cells reflects the interaction of nanoparticles with blood components.
The main aim of this study was to compare the effects of poly-ethylene-glycol (PEG)-oated and uncoated GNPs on the generation of reactive oxygen species (ROS); on the actions of distinct hepatotoxicity biomarkers such as alanine (ALT) and aspartate (AST) aminotransferases, and alkaline phosphatase (ALP); and on the histology of liver tissues in the rat model. Four distinct doses of PEG-coated and uncoated GNPs (12.5, 25, 50, and 100 µg/kg body weight) were used. Each group consisted of three rats receiving an oral administration of PEG-coated and uncoated GNPs for 5 days with one dose per 24 hours. The control group consisted of three rats that received deionized water. Twenty-four hours after the last treatment, samples were collected following standard procedures.
PEG-coated and uncoated GNPs enhanced the generation of ROS and the activity of serum aminotransferases (ALT/AST) and ALPs relative to the negative control. A liver histology assessment of GNP-exposed rats revealed statistically significant responses in the variation of the morphologies of tissues relative to those of the negative control. Nonetheless, uncoated GNPs demonstrated enhanced hepatotoxic outcomes relative to those of PEG-coated GNPs. The results demonstrated that both GNPs may be able to promote hepatotoxicity in Sprague Dawley rats through mechanisms of oxidative stress. However, uncoated GNPs have more harmful effects than PEG-coated GNPs relative to the negative control.
Taken together, the results of this study indicate that PEG-coated GNPs may be safer to use in nanomedicinal applications than uncoated GNPs. However, more studies must be performed to confirm the outcomes of PEGylation.
金纳米颗粒（GNPs）及其功能衍生物因其在许多生物医学应用中的重要性而备受关注。GNPs 越来越多地被纳入医学中的新诊断和治疗方法。因此，人们强烈推动充分了解它们与血液成分的相互作用。细胞的聚集反映了纳米颗粒与血液成分的相互作用。
本研究的主要目的是比较聚乙二醇（PEG）包覆和未包覆的 GNPs 对活性氧（ROS）生成的影响；对不同的肝毒性生物标志物如丙氨酸（ALT）和天冬氨酸（AST）氨基转移酶和碱性磷酸酶（ALP）的作用；以及对大鼠模型肝组织的组织学作用。使用了四种不同剂量的 PEG 包覆和未包覆的 GNPs（12.5、25、50 和 100μg/kg 体重）。每组由三只大鼠组成，每 24 小时口服一次 PEG 包覆和未包覆的 GNPs，连续 5 天。对照组由三只接受去离子水的大鼠组成。最后一次治疗后 24 小时，按照标准程序收集样品。
PEG 包覆和未包覆的 GNPs 相对于阴性对照增强了 ROS 的生成和血清氨基转移酶（ALT/AST）和 ALP 的活性。暴露于 GNP 的大鼠的肝组织学评估显示，与阴性对照相比，组织形态的变化存在统计学上的显著反应。然而，与 PEG 包覆的 GNPs 相比，未包覆的 GNPs 表现出更强的肝毒性作用。结果表明，两种 GNPs 都可能通过氧化应激机制在 Sprague Dawley 大鼠中促进肝毒性。然而，与阴性对照相比，未包覆的 GNPs 比 PEG 包覆的 GNPs 具有更大的有害影响。
综上所述，本研究结果表明，PEG 包覆的 GNPs 在纳米医学应用中可能比未包覆的 GNPs 更安全。然而，需要进行更多的研究来证实 PEG 化的结果。
