Release of copper complexes from a nanostructured sol–gel titania for cancer treatment

Copper complexes containing inorganic ligands were loaded on a functionalized titania (F-TiO₂) to obtain drug delivery systems. The as-received copper complexes and those released from titania were tested as toxic agents on different cancer cell lines. The sol–gel method was used for the synthesis and surface functionalization of the titania, as well as for loading the copper complexes, all in a single step. The resultant Cu/F-TiO₂ materials were characterized by several techniques. An “in vitro” releasing test was developed using an aqueous medium. Different concentrations (15.6–1000 µg mL⁻¹) of each copper complex, those loaded on titania (Cu/F-TiO₂), functionalized titania, and cis-Pt as a reference material, were incubated on RG2, C6, U373, and B16 cancer cell lines for 24 h. The morphology of functionalized titania and the different Cu/F-TiO₂ materials obtained consists of aggregated nanoparticles, which generate mesopores. The amorphous phase (in dominant proportion) and the anatase phase were the structures identified through the X-ray diffraction profiles. These results agree with high-resolution transmission electron microscopy. Theoretical studies indicate that the copper compounds were released by a Fickian diffusion mechanism. It was found that independently of the copper complex and also the cell line used, low concentrations of each copper compound were sufficient to kill almost 100 % of cancer cells. When the cancer cells were treated with increasing concentrations of the Cu/F-TiO₂ materials the number of survival cells decreased. Both copper complexes alone as well as those loaded on TiO₂ had higher toxic effect than cis-Pt.