Conclusion
Our results suggest that cationic methylated porphyrin derivatives are promising PDT photosensitizing agents. The epoxymethyl-containing derivatives showed increased efficacy relative to the neutral analogs, and are good candidates for further investigation. Lasers Surg. Med. 50:566-575, 2018. © 2018 Wiley Periodicals, Inc.
Methods
New porphyrins bearing cationic epoxymethylaryl groups were synthesized and characterized. Their cellular uptake, intracellular localization, and phototoxicity were evaluated in human HEp2 cells, and compared with their methylated analogs.
Results
All cationic porphyrins were efficient generators of singlet oxygen, with quantum yields in the range 0.35-0.61. The two methylated derivatives (3 and 4) accumulated the most within cells at all times investigated, up to 24 hours. Of these two porphyrins, 4 was the most phototoxic to the cells (LD50 = 2.4 μM at 1.5 J/cm2 ); however, porphyrin 3 also showed high phototoxicity (LD50 = 7.4 μM at 1.5 J/cm2 ). The epoxymethyl-containing porphyrins were found to be less phototoxic than the methylated derivatives, with LD50 > 38 μM. The neutral porphyrins showed no phototoxicity up to the 100 μM concentrations investigated, and had the lowest singlet oxygen quantum yields. All cationic porphyrins localized mainly in the cell ER, Golgi apparatus, and lysosomes.