ROS-generating TiO(2) nanoparticles for non-invasive sonodynamic therapy of cancer

The non-invasive photodynamic therapy has been limited to treat superficial tumours, primarily ascribed to poor tissue penetration of light as the energy source. Herein, we designed a long-circulating hydrophilized titanium dioxide nanoparticle (HTiO(2) NP) that can be activated by ultrasound to generate reactive oxygen species (ROS). When administered systemically to mice, HTiO(2) NPs effectively suppressed the growth of superficial tumours after ultrasound treatments. In tumour tissue, the levels of proinflammatory cytokines were elevated several fold and intense vascular damage was observed. Notably, ultrasound treatments with HTiO(2) NPs also suppressed the growth of deeply located liver tumours at least 15-fold, compared to animals without ultrasound treatments. This study provides the first demonstration of the feasibility of using HTiO(2) NPs as sensitizers for sonodynamic therapy in vivo.