A comparative study of toxicity of graphdiyne and graphene oxide to human umbilical vein endothelial cells

The success of graphene oxide (GO) has attracted extensive research interests in developing novel 2D nanomaterials (NMs). Graphdiyne (GDY) is a new member of carbon-based 2D NMs possessing sp- and sp(2)-hybridized carbon atoms. However, the toxicity of GDY is less investigated as GO. In this study, we compared the toxicity of GDY and GO with human umbilical vein endothelial cells (HUVECs). Exposure to up to 100-mu g/ml GDY and GO induced cytotoxicity, but there was no statistically significant difference between GDY and GO. At noncytotoxic concentration, 25-mu g/ml GDY or GO led to the internalization of NMs, typically in cytoplasm but not in nuclei. Only GO but not GDY significantly increased THP-1 adhesion onto NM-exposed HUVECs. Meanwhile, compared with GDY, GO more effectively promoted the release of soluble intracellular cell adhesion molecule-1 (sICAM-1), indicating the differential effects of GDY and GO on endothelial activation. Neither GDY nor GO induced intracellular superoxide. However, GO significantly promoted the expression of endoplasmic reticulum (ER) stress genes activating transcription factor 4 (ATF4) and X-box binding protein 1 spliced (XBP-1s), as well pyroptosis genes NLR family pyrin domain containing 3 (NLRP3) and gasdermin D (GSDMD), whereas GDY did not show this effect. The results suggested that GDY and GO could be internalized into HUVECs leading to cytotoxic effects. However, GO was more potent to activate endothelial activation probably due to the activation of ER stress and pyroptosis genes.