Quantum dots trigger immunomodulation of the NFκB pathway in human skin cells

The immunological effects of quantum dots are dependent on a variety of factors including, but not limited to, exposure time and dosing concentrations. In this study, we investigated the influence of 15 nm CdSe/ZnS-COOH quantum dot nanocrystals (QDs) on cell density, viability, and morphology in human epidermal keratinocytes (HEK) and human dermal fibroblasts (HDF). Furthermore, inflammatory and non-inflammatory immune responses were measured using protein and real time PCR array analysis from HDF cells exposed to predetermined sub-lethal concentrations of QDs. CdSe/ZnS-COOH QDs caused concentration-dependent (1-120 nM exposure concentrations) and time-dependent (8 h or 48 h) cell death, as evidenced by metabolic activity and morphological changes. QD exposure induced upregulation of apoptotic, inflammatory and immunoregulatory proteins such as TNF-α, IL-1B and IL-10. HMOX1, an indicator of stress due to reactive oxygen intermediates (ROIs) and/or metals, was upregulated at the later time point as well. QDs also caused modulation of genes known to be associated with inflammatory (IL1-β, CCL2, IRAK-2), immune (IL-1, IL-6, PGLYRP1, SERPINA1, IL-10), stress due to ROIs and/or heavy metals (HMOX1), and apoptotic (CASP1, ADORA2A) responses. Cellular effects from QD exposure were found to primarily follow the NFκB pathway. In addition, QDs induced a differential cytotoxicity in keratinocytes and fibroblasts at different exposure concentrations and time points, even at physiologically relevant dosing concentrations, thus emphasizing the need to investigate potential mechanisms of action among different cell types within the same target organ.