title: Novel Osmium-based Coordination Complexes as Photosensitizers for Panchromatic Photodynamic Therapy.
abstract: Cancer remains a major global malaise requiring the advent of new, efficient and low-cost treatments. Photodynamic therapy, which combines a photosensitizer and photons to produce cytotoxic reactive oxygen species, has been established as an effective cancer treatment but has yet to become mainstream. One of the main limitations has been the paucity of photosensitizers that are effective over a wide range of wavelengths, can exert their cytotoxic effects in hypoxia, are easily synthesized and produce few if any side effects. To address these shortfalls, three new osmium-based photosensitizers (TLD1822, TLD1824 and TLD1829) were synthesized and their photophysical and photobiological attributes determined. These photosensitizers are panchromatic (i.e. black absorbers), activatable from 200 to 900 nm and have strong resistance to photobleaching. In vitro studies show photodynamic therapy efficacy with both red and near-infrared light in normoxic and hypoxic conditions, which translated to good in vivo efficacy of TLD1829 in a subcutaneous murine colon cancer model.
authors.affiliation: Theralase Inc, Toronto, ON, Canada.
authors.forename: Savo
authors.initials: S
authors.lastname: Lazic
authors.affiliation: Theralase Inc, Toronto, ON, Canada.
authors.forename: Pavel
authors.initials: P
authors.lastname: Kaspler
authors.affiliation: Department of Chemistry, Acadia University, Wolfville, NS, Canada.
authors.forename: Ge
authors.initials: G
authors.lastname: Shi
authors.affiliation: Department of Chemistry, Acadia University, Wolfville, NS, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Monro
authors.affiliation: Department of Chemistry, Acadia University, Wolfville, NS, Canada.
authors.forename: Tariq
authors.initials: T
authors.lastname: Sainuddin
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Forward
authors.affiliation: Theralase Inc, Toronto, ON, Canada.
authors.forename: Kamola
authors.initials: K
authors.lastname: Kasimova
authors.affiliation: Department of Chemistry, Acadia University, Wolfville, NS, Canada.
authors.forename: Robie
authors.initials: R
authors.lastname: Hennigar
authors.affiliation: Theralase Inc, Toronto, ON, Canada.
authors.forename: Arkady
authors.initials: A
authors.lastname: Mandel
authors.affiliation: Department of Chemistry, Acadia University, Wolfville, NS, Canada.|Department of Chemistry and Biochemistry, The University of North Carolina at Greensboro, Greensboro, NC, USA.
authors.forename: Sherri
authors.initials: S
authors.lastname: McFarland
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.|Princess Margaret Cancer Centre, Toronto, ON, Canada.
authors.forename: Lothar
authors.initials: L
authors.lastname: Lilge
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D056831:Coordination Complexes / Q000737:chemistry* / Q000627:therapeutic use*; D051379:Mice; D009992:Osmium / Q000737:chemistry*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000627:therapeutic use*; D066244:Proton Magnetic Resonance Spectroscopy; D023041:Xenograft Model Antitumor Assays
chemical_list: D056831:Coordination Complexes; D017319:Photosensitizing Agents; D009992:Osmium