2018 年 76 巻 6 号 p. 566-574
Photodynamic inactivation (PDI) has received considerable attention as a methodology leading to the medical applications such as photodynamic therapy (PDT) for tumor cells. Porphyrin derivatives are attractive singlet-oxygen sensitizers for PDT because of their strong absorption band in the visible-light region. In general, free-base porphyrins comprise four Q-bands regions near 515, 550, 590, and 645 nm; these band regions have wider and longer wavelengths in comparison with that of the Q-bands of metalloporphyrins (560-610 nm). Therefore, most sensitizers for PDT are based on free-base porphyrins or chlorins (i.e. photofrin and laserphyrin). We have been interested in the use of phosphorus porphyrins (P-porphyrins) as photosensitizer. It is advantageous in P-porphyrins that water-solubilization is easily achieved through the modification of the axial ligands and the presence of these axial ligands also prevents the formation of porphyrin-ring aggregates. The aggregation may lower the water solubility of the porphyrins and retard the incorporation of the porphyrins into the target cell. This review is focused on the phosphorus porphyrin (1 and 2) modified by axial ligands such as -(CH2CH2O)m(CH2)nH and alkylpyridinium (APy) group, respectively. The PDI activities of 1 and 2 for Saccharomyces cerevisiae, Escherichia coli, and a human biliary cancer cell line (NOZ) have been evaluated using the half-life (T1/2 in min) of bacteria and the minimum effective concentrations ([P]) of the sensitizers. As the results, the [P] values for the PDI of S. cerevisiae was optimized to be 5 nM for 1e (m=2, n=6) and 1f (m=1, n=6). In the case of the PDI of NOZ cell, the IC50 for 1e was determined to be 37.6 nM which were one hundredth the IC50 (7.57 µM) for mono-l-aspartyl chlorin e6 (laserphyrin). The [P] values for S. cerevisiae were optimized to be 40 nM at 2h (alkyl=hexyl). In the case of the PDI of E. coli using 2, the PDI activity depends on the alkyl chain length of Apy. The [P] value for E. coli was optimized to be 250 nM (2b, alkyl=ethyl). Thus the P-porphyrins are applicable to the PDI of bacteria and cancer cells in low concentrations.