In vitro toxicity evaluation of dextran-functionalized graphene oxide nanoplatelets in human epidermal melanocytes...

Dextran-functionalized graphene oxide nanoplatelets (GONP-Dex) have demonstrated potential for use in diagnostic imaging and as MRI contrast agents, however, their toxicology on human exposure needs to be carefully assessed. To date, no study has explored their effects on human melanocytes, which are melanin-producing cells conferring multiple biological benefits in the skin, ears, eyes, hair, oral cavity, and brain. GONP-Dex (6.25-100 μg/mL) was examined for cytotoxicity on melanocytes from lightly pigmented (LP) and darkly pigmented (DP) human skin for a 48-h duration by trypan blue exclusion assay and Alamar Blue assay, while the cellular membrane integrity was tested using LDH assay. GONP-Dex impaired metabolic activity of LP and DP cells without lowering cell counts. LP and DP cells exposed to GONP-Dex showed higher cellular melanin in the absence of any alteration of cellular tyrosinase activity. However, GONP-Dex showed a concentration-dependent suppression of melanogenic differentiation; both dendrite numbers and lengths were inhibited in LP and DP cells, with a greater susceptibility in DP cells, indicative of the capacity of GONP-Dex to impair melanin export function. GONP-Dex induced oxidative stress in LP and DP cells by increasing intracellular reactive oxygen species (ROS), lowering mitochondrial membrane polarization (MMP), and augmenting nitrite production. Together, our novel results demonstrate a proof-of-principle study into the melanocytotoxic impact of GONP-Dex. Future studies to examine the cytotoxic effects of GONP-Dex using a physiological cell model consisting of melanocyte and keratinocyte coculture and a 3D skin tissue equivalent will help in further validating cytotoxicity.