Impact of particle size and surface modifications on the neurotoxic potential of copper oxide nanoparticles

Copper oxide (CuO) nanoparticles (NPs) have widespread applications in electronics, energy storage, and healthcare domains owing to their high surface-to-volume ratio, catalytic activity, and anti-bacterial and anti-microbial properties. However, the health hazard of direct CuO exposure to humans has raised safety concerns. CuO NPs can cross the blood-brain barrier, access the central nervous system, and trigger neurotoxicity. Previous studies have investigated the neurotoxicity of CuO NPs. However, the effects of different sizes and comparable size NPs with and without surface coating have not been previously reported. In this study, two differentially sized NPs (CuO-25 and CuO-48 NPs) and one polyvinylpyrrolidone-coated NP (CuO-P NPs; 46 nm) were synthesized and characterized. The neurotoxic potential of these NPs was examined in vitro using PC-12 cells. CuO NPs significantly decreased cell viability at concentrations of ≥ 1 μg/mL by inducing oxidative and nitrosative stress in a time-dependent and concentration-dependent manner. Additionally, CuO NPs altered mitochondrial membrane potential, upregulated Il6 and Tnf levels, induced apoptosis by upregulating Casp3 activity, and inhibited acetylcholinesterase activity. Furthermore, CuO NPs upregulated the expression of Maoa and Snca, which are associated with dopamine metabolism and the pathogenesis of neurodegenerative disorders. The three NPs exerted differential effects. The cytotoxic effects of CuO-25 NPs were higher than those of CuO-48 NPs. Additionally, the cytotoxic effects of coated NPs (CuO-P) were lower than those of uncoated NPs. Cu²⁺ ions released from NPs mediate the neurotoxic effects of NPs.