Targeted sonodynamic therapy using protein-modified TiO2 nanoparticles

Our previous study suggested new sonodynamic therapy for cancer cells based on the delivery of titanium dioxide (TiO2) nanoparticles (NPs) modified with a protein specifically recognizing target cells and subsequent generation of hydroxyl radicals from TiO2 NPs activated by external ultrasound irradiation (called TiO2/US treatment). The present study first examined the uptake behavior of TiO2 NPs modified with pre-S1/S2 (model protein-recognizing hepatocytes) by HepG2 cells for 24 h. It took 6 h for sufficient uptake of the TiO2 NPs by the cells. Next, the effect of the TiO2/US treatment on HepG2 cell growth was examined for 96 h after the 1 MHz ultrasound was irradiated (0.1 W/cm(2), 30 s) to the cells which incorporated the TiO2 NPs. Apoptosis was observed at 6 h after the TiO2/US treatment. Although no apparent cell-injury was observed until 24 h after the treatment, the viable cell concentration had deteriorated to 46% of the control at 96 h. Finally, the TiO2/US treatment was applied to a mouse xenograft model. The pre-S1/S2-immobilized TiO2 (0.1 mg) was directly injected into tumors, followed by 1 MHz ultrasound irradiation at 1.0 W/cm(2) for 60s. As a result of the treatment repeated five times within 13 days, tumor growth could be hampered up to 28 days compared with the control conditions. (C) 2011 Elsevier B.V. All rights reserved.