Evaluation of one- and two-photon activated photodynamic therapy with pyropheophorbide-a methyl ester in human cervical, lung and ovarian cancer cells.

Two-photon activated photodynamic therapy (2-γ PDT) has the potential of treating deeper tumors and/or improving tumor targeting. Here, we evaluated the one- and two-photon activated PDT efficacy of pyropheophorbide-a methyl ester (MPPa), a second-generation photosensitizer derived from chlorophyll a. We show that MPPa, when activated by femtosecond (fs) laser pulses at 674 nm, has high one-photon (1-γ) PDT efficacy against cisplatin-sensitive human cervical (HeLa) and cisplatin-resistant human lung (A549) and ovarian (NIH:OVCAR-3) cancer cells. At a low light dose of 0.06 J cm(-2), the IC50 (the MPPa concentration required to kill 50% of the cells) was determined to be 5.3 ± 0.3, 3.4 ± 0.3 and 3.6 ± 0.4 μM for HeLa, A549 and NIH:OVCAR-3 cells, respectively. More significantly, we also show that MPPa can be effectively activated by an 800 nm, 120 fs laser through 2-γ excitation; at a light dose causing no measurable photocytotoxicity in the absence of photosensitizer, the corresponding IC50 values were measured to be 4.1 ± 0.3, 9.6 ± 1.0 and 1.6 ± 0.3 μM, respectively. These results indicate that MPPa is a potent photosensitizer for both 1- and 2-γ activated PDT with potential applications for difficult-to-treat tumors by conventional therapies.