posted on 2020-03-12, 19:33authored byXiaojie Zhang, Xueling Guo, Xiaoxuan Kang, Hui Yang, Weiyi Guo, Lingmei Guan, Hai Wu, Libo Du
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.