Surface Functionalization of Pegylated Gold Nanoparticles with Antioxidants Suppresses Nanoparticle-Induced Oxidative Stress and Neurotoxicity

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.