Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines

Abstract

From its discovery, cisplatin therapy has widely been associated with toxicity and severe side effects. Platinum(IV) complexes, as well as immobilising them in nanomaterials could help to overcome these problems. Cyclooxygenase-2 (COX-2) is involved in cancer progresssion,1 which encourages the development of inhibitors of COX enzymes in antitumour therapy. To determine the potential cytotoxic effect, a cisplatin-ibuprofen conjugate in free form, as well as loaded into SBA-15 nanomaterial, was tested on 4T1, CT26, B16 and MC38 cell lines. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and crystal violet viability assays showed that both agents dose-dependently decreased the number of viable cells of all tested cell lines. Flow cytometric analysis revealed significant decrease in the division potential of B16-treated cells. In further investigations, activation of caspases proved by ApoStat assay was noticed; however, apoptosis was not identified by flow cytometry in culture of treated B16 cells. Finally, light microscopy evaluation revealed the presence of enlarged cells with prominent heterochromatin foci in nuclei upon the treatment indicating that cells entered senescent state. High antitumour potential defined at the nanomolar concentration on mouse melanoma cells make cisplatin-ibuprofen a suitable candidate for further research.