Catalytic nanomedicine technology: copper complexes loaded on titania nanomaterials as cytotoxic agents of cancer cell

Tessy Lopez,^1–3 Emma Ortiz-Islas,² Patricia Guevara,⁴ Esteban Gómez<sup>2

1</sup>Nanotechnology and Nanomedicine Laboratory, Metropolitan Autonomous University-Xochimilco, Coyoacán, México; ²Nanotechnology Laboratory, National Institute of Neurology and Neurosurgery "MVS," Tlalpan, México; ³Department of Chemical and Biomolecular Engineering, Tulane University, New Orleans, LA, USA; ⁴Neuroimmunology Laboratory, National Institute of Neurology and Neurosurgery "MVS," Tlalpan, México

Abstract: The anticancer properties of pure copper (II) acetate and copper (II) acetylacetonate, alone and loaded on functionalized sol-gel titania (TiO₂), were determined in four different cancer cell lines (C6, RG2, B16, and U373), using increasing concentrations of these compounds. The copper complexes were loaded onto the TiO₂ network during its preparation by the sol-gel process. Once copper-TiO₂ materials were obtained, these were characterized by several physical-chemical techniques. An in vitro copper complex–release test was developed in an aqueous medium at room temperature and monitored by ultraviolet spectroscopy. The toxic effect of the copper complexes, alone and loaded on TiO₂, was determined using a cell viability 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, when cancer cells were treated with increasing concentrations (15.75–1000 mg/mL) of these. Characterization studies revealed that the addition of copper complexes to the TiO₂ sol-gel network during its preparation, did not generate changes in the molecular structure of the complexes. The surface area, pore volume, and pore diameter were affected by the copper complex additions and by the crystalline phases obtained. The kinetic profiles of both copper complexes released indicated two different stages of release: The first one was governed by first-order kinetics and the second was governed by zero-order kinetics. The cell viability assay revealed a cytotoxic effect of copper complexes, copper-TiO₂, and cisplatin in a dose-dependent response for all the cell lines; however, the copper complexes exhibited a better cytotoxic effect than the cisplatin compound. TiO₂ alone presented a minor cytotoxicity for C6 and B16 cells; however, it did not cause any toxic effect on the RG2 and U373 cells, which indicates its high biocompatibility with these cells.

Keywords: functionalized-TiO₂, anticancer properties, toxic effect, cancer cell lines