INFLUENCE OF SUBSTITUTIONS IN ASYMMETRIC PORPHYRINS ON INTRACELLULAR UPTAKE, SUBCELLULAR LOCALIZATION AND PHOTOTOXICITY IN HELA CELLS

The asymmetric porphyrins with different substituents show various bioactivities in biomedical application. In this study, a series of asymmetric porphyrins with varying proportion of substituents, such as hydroxyphenyl and aminophenyl, were synthesized and characterized to evaluate their cell uptake, intracellular localization, cytotoxicities and phototoxicities in vitro. Among these synthesized porphyrins, 5-(4-aminophenyl)-10,15,20-tri-(4-hydroxyphenyl)-21,23H-porphyrin (porphyrin 5), which was mainly localized in mitochondria and with high quantum yields of singlet oxygen, is a potential candidate for photodynamic therapy. The effective phototoxicity of porphyrin 5 is mainly due to the higher extent in the cells and the selective mitochondria-localization. Comparing the partition coefficients of porphyrin derivatives, the best cellular uptake performs apparently with a partition coefficient (log p) ranging from about 1.7 to 1.9. In summary, higher quantum yields of singlet oxygen, and more specific mitochondrial localization of porphyrin 5 demonstrate its potential application in photodynamic therapy.