Sonodynamic Effect of Polyethylene glycol-conjugated Fullerene on Tumor

The objective of this study is to examine the tumoricidal activity of fullerene (C 60 ) when used in combination with ultrasound (US). The water-insoluble C 60 was chemically conjugated with poly(ethylene glycol) (PEG) to solubilize it in water. When mouse RLmale1 tumor cells were cultured in vitro with the C 60 -PEG conjugate, US irradiation to the cells suppressed the cell growth although the extent depended on the conjugate concentration and the irradiation conditions of US. The higher the conjugate concentration, the more strongly was the cell growth suppressed. The US-induced cytolytic effect was enhanced with an increase in the exposure time period and intensity while the effect was reduced with increased frequency. US irradiation made the conjugate generate superoxide anion (O 2 − ). It is likely that the light produced by US irradiation acts on the conjugate to induce O 2 − generation, resulting in the cytolytic effect on tumor cells. No growth suppression was observed when either the conjugate or US irradiation alone was applied. When the C 60 -PEG conjugate was intravenously injected into mice bearing tumor of the liver and the liver was percutaneously exposed to US, the mice survival period was significantly prolonged in contrast to either of them alone. The histological examination revealed that US irradiation following the conjugate injection suppressed the enlargement of tumor nodules in the liver. It is concluded that the combination of PEG-conjugated C 60 and US irradiation is promising for sonodynamic tumor therapy.