Tumor growth inhibition by sonodynamic therapy using a novel sonosensitizer

Sonodynamic therapy (SDT) with low-intensity ultrasound combined with a sonosensitizer may be a promising approach to cancer therapy. Use of ultrasound has the advantage of being noninvasive, with deep-penetration properties, and convenient because of the low or no sensitivity of sonosensitizers to light. In this study, SDT with a novel sonosensitizer (a porphyrin derivative) was evaluated in vitro and in vivo. Ultrasound irradiation with a sonosensitizer elicited potent sonotoxicity in vitro without the danger of phototoxicity. The sonotoxic effect was mediated by reactive oxygen species (ROS) and was reduced by ROS scavengers. Cell membrane lipid peroxidation increased significantly just after ultrasound irradiation with a sonosensitizer, but there was no increase in apoptosis. In an in vivo mouse xenograft model, SDT with a sonosensitizer markedly inhibited tumor cell growth. The skin hypersensitivity after light exposure was not observed in a sonosensitizer-treatment group, consistent with the in vitro findings. These results suggest that ROS generated by SDT with a sensitizer can damage tumor cells, resulting in necrosis and prevention of tumor growth. This noninvasive treatment with no adverse effects such as skin sensitivity is therefore promising for therapy of cancers located deep within patients.

Graphical AbstractSDT with DEG has potent sonotoxic effect by ROS production resulting in cell membrane lipid peroxidation and necrosis.Figure optionsDownload high-quality image (281 K)Download as PowerPoint slideHighlights
► DEG, a novel porphyrin derivative, has a potent sonotoxicity without phototoxicity.
► The sonotoxic effects of DEG are associated with necrosis but not apoptosis.
► Sonotoxicity of DEG is mediated by reactive oxygen species, resulting in membrane lipid peroxidation.
► Tumor growth is significantly inhibited by sonodynamic therapy (SDT) with DEG.
► SDT with DEG is a promising cure for deep tumors without skin sensitivity.