title: Exploitation of long-lived 3IL excited states for metal-organic photodynamic therapy: verification in a metastatic melanoma model.
abstract: Members of a family of Ru(II)-appended pyrenylethynylene dyads were synthesized, characterized according to their photophysical and photobiological properties, and evaluated for their collective potential as photosensitizers for metal-organic photodynamic therapy. The dyads in this series possess lowest-lying (3)IL-based excited states with lifetimes that can be tuned from 22 to 270 μs in fluid solution and from 44 to 3440 μs in glass at 77 K. To our knowledge, these excited-state lifetimes are the longest reported for Ru(II)-based dyads containing only one organic chromophore and lacking terminal diimine groups. These excited states proved to be extremely sensitive to trace amounts of oxygen, owing to their long lifetimes and very low radiative rates. Herein, we demonstrate that (3)IL states of this nature are potent photodynamic agents, exhibiting the largest photocytotoxicity indices reported to date with nanomolar light cytotoxicities at very short drug-to-light intervals. Importantly, these new agents are robust enough to maintain submicromolar PDT in pigmented metastatic melanoma cells, where the presence of melanin in combination with low oxygen tension is known to compromise PDT. This activity underscores the potential of metal-organic PDT as an alternate treatment strategy for challenging environments such as malignant melanoma.
authors.affiliation: Department of Chemistry, Acadia University , Wolfville, Nova Scotia B4P 2R6, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Lincoln
authors.forename: Lars
authors.initials: L
authors.lastname: Kohler
authors.forename: Susan
authors.initials: S
authors.lastname: Monro
authors.forename: Huimin
authors.initials: H
authors.lastname: Yin
authors.forename: Mat
authors.initials: M
authors.lastname: Stephenson
authors.forename: Ruifa
authors.initials: R
authors.lastname: Zong
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Chouai
authors.forename: Christopher
authors.initials: C
authors.lastname: Dorsey
authors.forename: Robie
authors.initials: R
authors.lastname: Hennigar
authors.forename: Randolph P
authors.initials: RP
authors.lastname: Thummel
authors.forename: Sherri A
authors.initials: SA
authors.lastname: McFarland
mesh_terms: D000328:Adult; D045744:Cell Line, Tumor; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology*; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D012428:Ruthenium