PEGylated CuInS2/ZnS quantum dots inhibit neurite outgrowth by downregulating the NGF/p75NTR/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 mu g/mL, they did not affect the survival rate of the PC12 cells. In addition, we found that CuInS2/ZnS-PEG QDs signifi-cantly 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.

Automated summary

The study revealed that PEGylated CuInS2/ZnS QDs did not affect the survival rate of neuron-like PC12 cells within a certain concentration range, but significantly inhibited neurite outgrowth and differentiation in the presence of NGF. The QDs were found to downregulate the expression of low-affinity NGF receptor and negatively regulate the downstream MAPK cascade.