Photosensitized Protein-Damaging Activity, Cytotoxicity, and Antitumor Effects of P(V)porphyrins Using Long-Wavelength Visible Light through Electron Transfer

Photodynamic therapy (PDT) is a less-invasive treatment for cancer through the administration of less-toxic porphyrins and visible-light irradiation. Photosensitized damage of biomacromolecules through singlet oxygen (¹O₂) generation induces cancer cell death. However, a large quantity of porphyrin photosensitizer is required, and the treatment effect is restricted under a hypoxic cellular condition. Here we report the phototoxic activity of P­(V)­porphyrins: dichloroP­(V)­tetrakis­(4-methoxyphenyl)­porphyrin (CLP­(V)­TMPP), dimethoxyP­(V)­tetrakis­(4-methoxyphenyl)­porphyrin (MEP­(V)­TMPP), and diethyleneglycoxyP­(V)­tetrakis­(4-methoxyphenyl)­porphyrin (EGP­(V)­TMPP). These P­(V)­porphyrins damaged the tryptophan residue of human serum albumin (HSA) under the irradiation of long-wavelength visible light (>630 nm). This protein photodamage was barely inhibited by sodium azide, a quencher of ¹O₂. Fluorescence lifetimes of P­(V)­porphyrins with or without HSA and their redox potentials supported the electron-transfer-mediated oxidation of protein. The photocytotoxicity of these P­(V)­porphyrins to HeLa cells was also demonstrated. CLP­(V)­TMPP did not exhibit photocytotoxicity to HaCaT, a cultured human skin cell, and MEP­(V)­TMPP and EGP­(V)­TMPP did; however, cellular DNA damage was barely observed. In addition, a significant PDT effect of these P­(V) porphyrins on a mouse tumor model comparable with the traditional photosensitizer was also demonstrated. These findings suggest the cancer selectivity of these P­(V)­porphyrins and lower carcinogenic risk to normal cells. Electron-transfer-mediated oxidation of biomacromolecules by P­(V)­porphyrins using long-wavelength visible light should be advantageous for PDT of hypoxic tumor