Phototoxicity of Mesoporous TiO2 + Gd Microbeads With Theranostic Potential
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.