Graphene Oxide Quantum Dots Reduce Oxidative Stress and Inhibit Neurotoxicity In Vitro and In Vivo through Catalase-Like Activity and Metabolic Regulation

Abstract

Both oxidative stress and neurotoxicity are huge challenges to human health, and effective methods and agents for resisting these adverse effects are limited, especially in vivo. It is shown here that, compared to large graphene oxide (GO) nanosheets, GO quantum dots (GOQDs), as nanozymes, efficiently reduce reactive oxygen species (ROS) and H2O2 in 1-methyl-4-phenyl-pyridinium ion (MPP+)-induced PC12 cells. In addition, GOQDs exert neuroprotective effects in a neuronal cell model by decreasing apoptosis and α-synuclein. GOQDs also efficiently diminish ROS, apoptosis, and mitochondrial damage in zebrafish treated with MPP+. Furthermore, GOQDs-pretreated zebrafish shows increased locomotive activity and Nissl bodies in the brain, confirming that GOQDs ameliorate MPP+-induced neurotoxicity, in contrast to GO nanosheets. GOQDs contribute to neurotoxic amelioration by increasing amino acid metabolism, decreasing tricarboxylic acid cycle activity, and reducing steroid biosynthesis, fatty acid biosynthesis, and galactose metabolic pathway activity, which are related to antioxidation and neurotransmission. Meanwhile, H2O2 decomposition and Fenton reactions suggest the catalase-like activity of GOQDs. GOQDs can translocate into zebrafish brains and exert catalase-mimicking activity to resist oxidation in the intracellular environment. Unlike general nanomaterials, biocompatible GOQDs demonstrate their high potential for human health by reducing oxidative stress and inhibiting neurotoxicity.

 

http://onlinelibrary.wiley.com/doi/10.1002/advs.201700595/full