Abstract
Cu2-x Se nanoparticles (Cu2-x Se NPs) are widely used for optical diagnostic imaging and photothermal therapy due to their strong near-infrared (NIR) optical absorption. With the continuous expansion of applications using Cu2-x Se NPs, their biosafety has received increasing attention in recent years. Cu2-x Se NPs can enter the brain by crossing the blood-brain barrier, but the neurotoxicity of NPs remains unclear. The present investigation provides direct evidence that the toxicity of Cu2-x Se NPs can be specifically exploited to kill rat pheochromocytoma PC-12 cells (a cell line used as an in vitro model for brain neuron research) in dose- and time-dependent manners. These cytotoxicity events were accompanied by mitochondrial damage, adenosine triphosphate (ATP) depletion, production of oxidizing species (including reactive oxygen species (ROS), malondialdehyde (MDA) and hydrogen peroxide (H2O2)), as well as reductions in antioxidant defense systems (glutathione (GSH) and superoxide dismutase (SOD)). Moreover, our in vivo study also confirmed that Cu2-x Se NPs markedly induced neurotoxicity and oxidative stress damage in the striatum and hippocampal tissues of BALB/c mice. These findings suggest that Cu2-x Se NPs induce neurotoxicity in PC-12 cells and BALB/c mice via oxidative stress damage, which provides useful information for understanding the neurotoxicity of Cu2-x Se NPs.