Surface Functionalization of Pegylated Gold Nanoparticles with Antioxidants Suppresses Nanoparticle-Induced Oxidative Stress and Neurotoxicity.
Xiaojie ZhangXueling GuoXiaoxuan KangHui YangWeiyi GuoLingmei GuanHai WuLi-Bo DuPublished in: Chemical research in toxicology (2020)
Because of their biocompatibility and biosafety, pegylated Au NPs (Au@PEG), as a nanodrug-carrier, have been widely applied in different biomedical applications, including imaging and drug delivery systems. Under such conditions, the biosafety of Au@PEG has attracted tremendous attention. However, only a small number of studies focused on the neurotoxicity of Au@PEG used as drug delivery carriers not to mention reducing the neurotoxicity of Au@PEG. To address this issue, the adverse effects of Au@PEG on human neuroblastoma SHSY5Y cells were first investigated. The results showed that 4.5 nm Au@PEG significantly induced cell apoptosis through upregulating reactive oxygen species (ROS) production and disordering the mitochondrial membrane potential. To further evaluate whether the neurotoxicity of Au@PEG could be improved through conjugating antioxidants on the surface of Au@PEG, Trolox (a vitamin E analogue)-functionalized Au@PEG (Au@Trolox) was synthesized. The results showed that the neurotoxicity of Au@PEG on SHSY5Y cells could be significantly improved by Au@Trolox. Next, mice were subjected to administration of 4.5 nm Au@PEG and Au@Trolox for 3 months. An increase of oxidative stress and a decrease in the activity of key antioxidant enzymes including glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) were observed after long-term injection of Au@PEG. More importantly, both the apoptosis of neurons and the activation of astrocytes were observed in the hippocampus of mice injected with Au@PEG. In contrast, the adverse effects of Au@PEG could be improved when injected with Au@Trolox. In short, the present study provided new insights into the toxicity evaluation of nanoparticles and would help to better understand and prevent the neurotoxicity of nanomaterials used in pharmaceutics.
Keyphrases
- sensitive detection
- drug delivery
- reduced graphene oxide
- oxidative stress
- gold nanoparticles
- reactive oxygen species
- visible light
- signaling pathway
- induced apoptosis
- dna damage
- hydrogen peroxide
- metabolic syndrome
- magnetic resonance imaging
- endothelial cells
- spinal cord
- cancer therapy
- computed tomography
- cell death
- cell proliferation
- mass spectrometry
- drug release
- working memory
- climate change
- photodynamic therapy
- insulin resistance