PEGylated CuInS₂/ZnS quantum dots inhibit neurite outgrowth by downregulating the NGF/p75^NTR/MAPK pathway

The widespread application of cadmium-free CuInS₂/ZnS QDs has raised great concern regarding their potential toxicity to humans. To date, toxicological data related to CuInS₂/ZnS QDs are scarce. Neurons play extraordinary roles in regulating the activities of organs and systems, and serious consequences occur when neurons are damaged. Currently, the potential toxicity of CuInS₂/ZnS QDs on neurons has not been fully elucidated. Here, we investigate the neurotoxicity of PEGylated CuInS₂/ZnS (CuInS₂/ZnS-PEG) QDs on neuron-like PC12 cells. We found that CuInS₂/ZnS-PEG QDs were taken up by PC12 cells, but at a concentration range from 0 to 100 μg/mL, they did not affect the survival rate of the PC12 cells. In addition, we found that CuInS₂/ZnS-PEG QDs significantly inhibited neurite outgrowth from and the differentiation of PC12 cells in the presence of NGF, while COOH-modified CuInS₂/ZnS QDs or free PEG did not have a similar effect. Further studies showed that CuInS₂/ZnS-PEG QDs obviously downregulated the expression of low-affinity NGF receptor (p75^NTR) and subsequently negatively regulated the downstream MAPK cascade by dephosphorylating ERK1/2 and AKT. Taken together, these results suggest that CuInS₂/ZnS-PEG QDs disturb NGF signal transduction from external stimuli to relevant internal signals, thus affecting normal biological processes such as neurite outgrowth and cell differentiation.