Sonodynamic therapy of cancer using a novel porphyrin derivative, DCPH‐P‐Na(I), which is devoid of photosensitivity

• Published in: Cancer science Vol. 98; no. 6; pp. 916 - 920
• Main Authors: Hachimine, Ken, Shibaguchi, Hirotomo, Kuroki, Motomu, Yamada, Hiromi, Kinugasa, Tetsushi, Nakae, Yoshinori, Asano, Ryuji, Sakata, Isao, Yamashita, Yuichi, Shirakusa, Takayuki, Kuroki, Masahide
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Publishing Asia 01.06.2007; Blackwell
• Subjects: Animals; Biological and medical sciences; Cell Line, Tumor; Dermatology; Humans; Medical sciences; Mice; Mice, Inbred BALB C; Neoplasms - therapy; Original; Photochemotherapy - adverse effects; Photochemotherapy - methods; Porphyrins - administration & dosage; Porphyrins - chemistry; Porphyrins - therapeutic use; Reactive Oxygen Species - analysis; Skin involvement in other diseases. Miscellaneous. General aspects; Spectrophotometry; Tumors; Ultrasonics - adverse effects; Xenograft Model Antitumor Assays; Photosensitivity; Skin disease; Cancerology; Treatment; Malignant tumor; Porphyrin derivatives; Cancer
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/j.1349-7006.2007.00468.x

To improve the efficacy of sonodynamic therapy of cancer using photosensitizers, we developed a novel porphyrin derivative designated DCPH‐P‐Na(I) and investigated its photochemical characteristics and sonotoxicity on tumor cells. DCPH‐P‐Na(I) exhibited a minimum fluorescent emission by excitation with light, compared with a strong emission from ATX‐70, which is known to reveal both photo‐ and sonotoxicity. According to this observation, when human tumor cells were exposed to light in the presence of DCPH‐P‐Na(I) in vitro, the least phototoxicity was observed, in contrast to the strong phototoxicity of ATX‐70. However, DCPH‐P‐Na(I) exhibited a potent sonotoxicity on tumor cells by irradiation with ultrasound in vitro. This sonotoxicity was reduced by the addition of L‐histidine, but not D‐mannitol, thus suggesting that singlet oxygen may be responsible for the sonotoxicity of DCPH‐P‐Na(I). DCPH‐P‐Na(I) demonstrated significant sonotoxicity against a variety of cancer cell lines derived from different tissues. In addition, in a mouse xenograft model, a potent growth inhibition of the tumor was observed using sonication after the administration of DCPH‐P‐Na(I) to the mouse. These results suggest that sonodynamic therapy with DCPH‐P‐Na(I) may therefore be a useful clinical treatment for cancers located deep in the human body without inducing skin sensitivity, which tends to be a major side‐effect of photosensitizers. (Cancer Sci 2007; 98: 916–920)