Sonodynamic therapy of cancer using a novel porphyrin derivative, DCPH-P-Na(I), which is devoid of photosensitivity.
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.
Hachimine
Ken
K
Department of Biochemistry, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
Shibaguchi
Hirotomo
H
Kuroki
Motomu
M
Yamada
Hiromi
H
Kinugasa
Tetsushi
T
Nakae
Yoshinori
Y
Asano
Ryuji
R
Sakata
Isao
I
Yamashita
Yuichi
Y
Shirakusa
Takayuki
T
Kuroki
Masahide
M
D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000628:therapy*; D010778:Photochemotherapy / Q000009:adverse effects / Q000379:methods*; D011166:Porphyrins / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000032:analysis; D013053:Spectrophotometry; D014465:Ultrasonics / Q000009:adverse effects; D023041:Xenograft Model Antitumor Assays
C521512:13,17-bis(1-carboxyethyl)-8-(2-(2,4-dichlorophenylhydrazono)ethylidene)-3-ethenyl-7-hydroxy-2,7,12,18-tetramethylchlorin; D011166:Porphyrins; D017382:Reactive Oxygen Species; C081908:ATX 70