title: Evaluation of one- and two-photon activated photodynamic therapy with pyropheophorbide-a methyl ester in human cervical, lung and ovarian cancer cells.
abstract: 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.
authors.affiliation: Department of Physics and Astronomy, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada.
authors.forename: Ting
authors.initials: T
authors.lastname: Luo
authors.affiliation: Department of Medical Biophysics, University of Toronto, and Ontario Cancer Institute, 610 University Avenue, Toronto, ON M5G 2M9, Canada.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wilson
authors.affiliation: Department of Physics and Astronomy, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada; Departments of Biology and Chemistry, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada. Electronic address: qblu@uwaterloo.ca.
authors.forename: Qing-Bin
authors.initials: QB
authors.lastname: Lu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008027:Light; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010778:Photochemotherapy; D017785:Photons; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; C452939:pyropheophorbide-a methylester
keywords: Cisplatin-resistance; Femtosecond laser; Near-infrared light; Photodynamic therapy (PDT); Pyropheophorbide-a methyl ester