Study of cancer cell cytotoxicity, internalization and modulation of growth factors induced by transferrin-conjugated formulations of metallodrug-functionalized mesoporous silica nanoparticles

Abstract

Nano-sized materials have shown to have very high potential in anticancer therapy by an adequate tuning of their functionalization and physico-chemical properties. This study is focused on the synthesis and characterization of mesoporous silica nanoparticles (MSN) functionalized with a titanium(IV) or an organotin(IV) compound (therapeutic agents), fluorescein isothiocyanate (image agent) and transferrin (targeting molecule). The analysis of the biological activity of the metallodrug-functionalized systems with and without transferrin has been evaluated and the cell internalization with respect to the presence of the protein has been assessed. The biological results show, as expected, that Sn-based materials are more active than the Ti-based systems with some of the tin-functionalized nanoparticles being almost 50 times more active than carboplatin. In contrast, the cellular uptake seems to be higher in Ti-based materials, which take advantage of the stronger interaction with transferrin to internalize the cells with more effectivity. Finally, a study of vascular endothelial growth factor A (VEGF-A), human fibroblast growth factor 2 (FGF-2) and nuclear factor κβ transcription factor (NF-κβ) show that, specially the Sn-based MSNs, were able to modulate these factors in A2780 cells showing anti-angiogenic effects through VEGF-A and FGF-2, probably due to interaction of the materials with transferrin.