Zinc Coproporphyrin I Derived from Meconium Has an Antitumor Effect Associated with Singlet Oxygen Generation

Abstract

Introduction: Zinc coproporphyrin I (ZnCP-I) is a photosensitive molecule and a major component of meconium. Here, we examined the effects of ZnCP-I as a potential photosensitizer in photodynamic therapy for tumors. Materials and Methods: (1) Aqueous ZnCP-I was irradiated with a pulsed YAG-SHG laser (wavelength: 532 nm)/YAG-SHG dye laser (wavelength: 566 nm). (2) HeLa cells were incubated in 200 m<smlcap>M</smlcap> ZnCP-I, and accumulation of ZnCP-I in HeLa cells was evaluated with ZnCP-I-specific fluorescence over 500 nm. (3) Aqueous ZnCP-I was administered intravenously to HeLa tumor-bearing mice at a dose of 10.2 mg/kg body weight. The tumors were irradiated with a filtered halogen lamp (wavelength: 580 nm) at 100 J/cm² 20 min after administration. Results: (1) An intense near-infrared emission spectrum was observed at around 1,270 nm after irradiation. The emission intensity was proportional to the laser power between 10 and 80 mW and was completely inhibited by addition of NaN₃, a singlet oxygen scavenger. (2) ZnCP-I-specific fluorescence was detected in the HeLa cell cytoplasm. (3) Irradiated tumors treated with ZnCP-I were mostly necrotized. Conclusion: ZnCP-I accumulated in tumor cells, produced singlet oxygen upon irradiation, and necrotized the tumor cells. These results suggest that ZnCP-I may be an effective photosensitizer.