Production of singlet oxygen on irradiation of a photodynamic therapy agent, zinc-coproporphyrin III, with low host toxicity.
Zinc-coproporphyrin III (Zincphyrin) acts efficiently as a photodynamic therapy (PDT) agent in mice, while it shows no tumor cell-killing activity in vitro and has a high LD50 (low toxicity) in mice. It appears to have advantages over other porphyrins as a practical PDT reagent. In order to examine the action mechanism of Zincphyrin in PDT, we evaluated the photochemical characteristics of Zincphyrin by measurement of the near-infrared emission at 1268 nm, which provides direct evidence for formation of 1O2. Intense emission was observed in the presence of Zincphyrin, and was completely inhibited by NaN3, a 1O2 scavenger. Based on a quenching study, the rate constant of the reaction of 1O2 with NaN3 was determined to be 1.5-3.5 M(-1) s(-1), which is close to the reported value (3.8 x 10(8) M(-1) s(-1)). The intensity of the 1O2-specific emission was proportional to both the laser power and the concentration of Zincphyrin. The fluorescence quantum yield of Zincphyrin was 0.004 in phosphate buffer (100 mM, pH 7.4), which indicates that the excited state decays via other pathway(s) faster than through the fluorescence emission pathway. The lifetime of the triplet state of Zincphyrin (210 micros) was relatively long compared to that of other porphyrins, such as hematoporphyrin (Hp) (40 micros), coproporphyrin I (50 gs), or coproporphyrin III (36 gs). These results demonstrate the photodynamic generation of 1O2 by Zincphyrin.
Yamamoto
Megumi
M
Department of Basic Medical Sciences, National Institute for Minamata Disease, 4058-18 Hama, Minamata, Kumamoto 867-0008, Japan. yamamoto@nimd.go.jp
Nagano
Tetsuo
T
Okura
Ichiro
I
Arakane
Kumi
K
Urano
Yasuteru
Y
Matsumoto
Kazuhiko
K
D003306:Coproporphyrins / Q000737:chemistry* / Q000528:radiation effects*; D015394:Molecular Structure; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000528:radiation effects; D026082:Singlet Oxygen / Q000737:chemistry* / Q000528:radiation effects*; D015032:Zinc / Q000737:chemistry* / Q000528:radiation effects*
D003306:Coproporphyrins; D017319:Photosensitizing Agents; C026971:coproporphyrin III; D026082:Singlet Oxygen; D015032:Zinc