The toxicity of multi-walled carbon nanotubes (MWCNTs) to human endothelial cells: The influence of diameters of MWCNTs

The biological applications of multi-walled carbon nanotubes (MWCNTs) may lead to their exposure to human blood vessels, but the influence of their physicochemical properties on toxicity to endothelial cells is incompletely known. Here, human umbilical vein endothelial cells (HUVECs) were exposed to three commercially available MWCNTs, namely XFM4, XFM22, and XFM34 (diameters XFM4 < XFM22 < XFM34), to understand the possible role of their diameter on toxicity. Based on the same mass concentration, XFM4 induced significantly higher level of cytotoxicity than the other two MWCNTs, and HUVECs internalized more XFM4. Cytokine release, monocyte adhesion, and intracellular reactive oxygen species levels were significantly induced only after XFM4 treatment. The exposure to XFM4 significantly reduced the expression of autophagic genes autophagy-related 7 (ATG7), autophagy-related 12 (ATG12), and beclin 1 (BECN1) and increased the expression of endoplasmic reticulum (ER) stress genes DNA damage inducible transcript 3 (DDIT3) and X-box binding protein 1 spliced (XBP-1s). Moreover, the modulation of autophagy-ER stress by chemicals resulted in a significant increase in the cytotoxicity of XFM4 but had minimal impact on the cytotoxicity of XFM34. These data indicate that the diameter of MWCNTs may influence their toxicity to HUVECs, probably through autophagy dysfunction and ER stress.