Development of a new surgical strategy in tumor resection for malignant bone and soft tissue tumors with cytocidal effect of acridine orange excited by various dynamic energy-wave.

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In this study, we have undertaken to develop a new surgical strategy in tumor resection for malignant bone and soft tissue tumors, using cytocidal effect by acridine orange (AO) excited by various dynamic energy waves such as light-beam, X-ray, electro-magnetic field or ultra-sound. In vitro study using mouse osteosarcoma cell line revealed that AO excited with blue light beam (466 nm) or low-dose X-ray (5 Gy) showed a strong cytocidal effect, although both of an electro-magnetic field stimulation and ultra-sound did not. AO excited with blue light or X-ray was also effective to inhibit tumor growth in vivo study using mouse osteosarcoma inoculated subcutaneously. The mechanism of such a strong cytocidal effect of AO is speculated that intracellular free-radical as singlet oxygen which subsequently occurred after AO excitation with blue light or X-ray may kill tumor cells. We also found that AO has a biological feature to specifically accumulate into malignant tumor cells, especially, malignant bone and soft tissue tumors. Based on these results, at present, we clinically apply photodynamic therapy and radiodynamic therapy with AO to marginal or intra-lesional resection of malignant bone and soft tissue tumors.