Kononenko V, Imani R, Repar N, Benčina M, Lorenzetti M, Erman A, Drobne D, Iglič A
[ site ] Advances in Biomembranes and Lipid Self-Assembly, 2017

Cancer theranostic is an approach that combines cancer diagnostic and therapeutic capabilities into a single agent. We synthesized Gadolinium-doped mesoporous TiO₂ microbeads (TiO₂ + xGd MBs; x = 0%, 5%, and 10%), which can be used as a contrast agent in magnetic resonance imaging and as a photosensitizer in photodynamic therapy. Human osteosarcoma MG-63 cells were used as an in vitro model for cancer cells. In preliminary experiments, we studied the cytotoxicity of TiO₂ + xGd MBs with different Gd contents (0%, 5%, and 10%). To study cellular internalization of different TiO₂ + xGd MBs, differential interference microscopy and transmission electron microscopy were performed. Phototoxicity of Gd-doped TiO₂ MBs (TiO₂ + 5%Gd and TiO₂ + 10%Gd MBs) was evaluated and compared with undoped TiO₂ MBs to determine if Gd-doping can be used to design TiO₂ MBs for theranostic medicinal purposes. The viability of MG-63 cells exposed to TiO₂ + xGd MBs and UV-A radiation was examined by resazurin assay, neutral red uptake assay, and differential staining using propidium iodide and Hoechst 33342. All the tested TiO₂ + xGd MBs were internalized by MG-63 cells and significantly reduced cell viability after 3 min UV-A radiation, while the viability of untreated cells was unaffected by 3 min radiation. Moreover, our results show that MG-63 cells internalize TiO₂ + 5%Gd MBs and TiO₂ + 10%Gd MBs to a much greater extent than undoped TiO₂ MBs, which resulted in higher phototoxicity of Gd-doped TiO₂ MBs. These outcomes suggest that Gd-doped TiO₂ MBs have a potential use in theranostic medicine.