Fabrication and toxicity characterization of a hybrid material based on oxidized and aminated MWCNT loaded with carboplatin

Abstract

This study focused on the fabrication and toxicity characterization of a hybrid material-based on the multiple functionalizations of multiwalled carbon nanotubes (MWCNTs) with carboxyl or amino groups and the anti-tumor drug carboplatin (CP). The functionalization was evidenced by Fourier transformed infrared spectroscopy (FTIR) and high performance liquid chromatography (HPLC). The amount of platinum ions released in the simulated body fluid (SBF) was assessed by inductively coupled plasma mass spectrometry (ICP-MS). Cell viability, nanotubes cellular uptake, cell proliferation, superoxide anion production, SOD activity, intracellular glutathione and protein expression of several molecules involved in breast tumor cell survival and death were investigated after 24h exposure. Exposure to the aminated carbon nanotubes loaded with carboplatin resulted in a greater decrease of viability compared to oxidized carbon nanotubes loaded with the same drug, which was in an inversely proportional relationship with the production of superoxide anions in breast cancer cells. The inhibition of Hsp60, Hsp90, p53 and Mdm2 protein expression was induced as a consequence of the cytoprotection mechanism failure. Overexpression of Beclin1 and the reduction of Bcl2 expression were also observed, suggesting that functionalized MWCNT loaded with CP trigger cell death via autophagy in breast cancer cells.

Keywords: Autophagy; Carboplatin; Cellular uptake; Heat shock proteins; ICP-MS; MWCNTs.