InP/ZnS Quantum Dots Cause Inflammatory Response in Macrophages Through Endoplasmic Reticulum Stress and Oxidative stress

PURPOSE: Quantum dots (QDs) are widely used semiconductor nanomaterials. Indium phosphide/zinc sulfide (InP/ZnS) QDs are becoming potential alternatives to toxic heavy metal-containing QDs. However, the potential toxicity and, in particular, the immunotoxicity of InP/ZnS QDs are unknown. This study aimed to investigate the impacts of InP/ZnS QDs on inflammatory responses both in vivo and in vitro. METHODS: Mice and mouse bone marrow-derived macrophages (BMMs) were exposed to polyethylene glycol (PEG) coated InP/ZnS QDs. The infiltration of neutrophils and the release of interleukin-6 (IL-6) were measured using a hematology analyzer and an enzyme-linked immunosorbent assay (ELISA) for the in vivo test. Cytotoxicity, IL-6 secretion, oxidative stress and endoplasmic reticulum (ER) stress were studied in the BMMs, and then, inhibitors of oxidative stress and ER stress were used to explore the mechanism of the InP/ZnS QDs. RESULTS: We found that 20 mg/kg PEG-InP/ZnS QDs increased the number of neutrophils and the levels of IL-6 in both peritoneal lavage fluids and blood, which indicated acute phase inflammation in the mice. PEG-InP/ZnS QDs also activated the BMMs and increased the production of IL-6. In addition, PEG-InP/ZnS QDs triggered oxidative stress and the ER stress-related PERK-ATF4 pathway in the BMMs. Moreover, the inflammatory response caused by the PEG-InP/ZnS QDs could be attenuated in the macrophages by blocking the oxidative stress or the ER stress with inhibitors. CONCLUSION: InP/ZnS QDs can activate macrophages and induce acute phase inflammation both in vivo and in vitro, which may be regulated by oxidative stress and ER stress. Our present work is expected to help clarify the biosafety of InP/ZnS QDs and promote their safe application in biomedical and engineering fields.