Photodynamic therapy targeted to tumor-induced angiogenic vessels.
Cancer photodynamic therapy (PDT) with benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) may be effective not only by being directly cytotoxic to tumor cells, but also by being cytotoxic to the endothelium of tumor neovasculature. In the present study, we investigated the effect of PDT with an experimental liposomal formulation of BPD-MA on tumor-induced angiogenic vessels using a murine dorsal air sac model. First, hemostasis of neovasculature was examined by varying the regimen of PDT. Laser irradiation at 15 min after injection of 2 mg/kg liposomal BPD-MA (15 min PDT) caused complete blocking of blood flow in neovasculature. In contrast, PDT did not inhibit blood flow when the irradiation occurred 3 h after the injection of liposomal BPD-MA (3 h PDT). Next, the antitumor effect of PDT on Meth A sarcoma-bearing mice was investigated by using the hemostasis-inducing regimen. Tumor growth was strongly inhibited after the 15 min PDT with BPD-MA at a dose of 0.5-2 mg/kg. In contrast, 3 h PDT with BPD-MA at a dose of 2 mg/kg suppressed tumor growth only partially. The current study indicates that 15 min PDT causes strong suppression of tumor growth, perhaps through damaging endothelial cells in the tumor neovasculature rather than through a direct cytotoxic effect on tumor cells.
Kurohane
K
K
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Yada, 422-8526, Shizuoka, Japan.
Tominaga
A
A
Sato
K
K
North
J R
JR
Namba
Y
Y
Oku
N
N
D000818:Animals; D004195:Disease Models, Animal; D008081:Liposomes; D008297:Male; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011166:Porphyrins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012513:Sarcoma, Experimental / Q000098:blood supply* / Q000139:chemically induced / Q000378:metabolism; D012867:Skin / Q000098:blood supply; D014018:Tissue Distribution
D008081:Liposomes; D017319:Photosensitizing Agents; D011166:Porphyrins; C504224:benzoporphyrin D; D008748:Methylcholanthrene