The response of peritoneal macrophages to dapsone covalently attached on the surface of carbon nanotubes

Abstract

Dapsone is an anti-microbial and anti-inflammatory drug. Water-dispersible dapsone-modified multi-wall carbon nanotubes (dap-MWCNTs) were prepared by chemical modification of the carboxyl groups introduced on the surface of the nanotubes using O-(7-aza-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (N-HATU) and N,N-diisopropylethylamine (DIEA). The modification was confirmed by Fourier-transform infrared spectroscopy, transmission election microscopy and thermogravimetric analysis. The biological effect of dap-MWCNTs was tested using rat peritoneal macrophages (PMempty set). By confocal laser microscopy and flow cytometry, it was shown that the dap-MWCNTs were rapidly ingested by PMempty set as were the control, oxidized o-MWCNTs. Neither dap-MWCNTs at lower concentrations (up to 50 mu g/ml), nor o-MWCNTs, at equivalent concentrations, respectively affected the viability of PMempty set, while higher concentrations triggered apoptosis. Apoptosis of PMempty set induced by the control, o-MWCNTs, was higher than that induced by dap-MWCNTs and it correlated with the induction of oxidative stress. In contrast, dap-MWCNTs did not trigger oxidative stress but caused apoptosis of PMempty set predominantly after prolonged cultivation (3 days). Although equivalent concentrations of soluble dapsone induced oxidative stress, they were anti-apoptotic. Cumulatively, the obtained results show the complexity of dap-MWCNT/PMempty set interactions and suggest that this complex could be investigated for the treatment of dapsone-sensitive intracellular microorganisms or inflammatory diseases responding to dapsone therapy.