Exploitation of Long-Lived 3IL Excited States for Metal鈥揙rganic Photodynamic Therapy: Verification in a Metastatic Melanoma Model

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• 作者：Richard Lincoln ; Lars Kohler ; Susan Monro ; Huimin Yin ; Mat Stephenson ; Ruifa Zong ; Abdellatif Chouai ; Christopher Dorsey ; Robie Hennigar ; Randolph P. Thummel ; Sherri A. McFarland
• 刊名：Journal of the American Chemical Society
• 出版年：2013
• 出版时间：November 13, 2013
• 年：2013
• 卷：135
• 期：45
• 页码：17161-17175
• 全文大小：521K
• 年卷期：v.135,no.45(November 13, 2013)
• ISSN：1520-5126

文摘

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鈥搊rganic photodynamic therapy. The dyads in this series possess lowest-lying ³IL-based excited states with lifetimes that can be tuned from 22 to 270 渭s in fluid solution and from 44 to 3440 渭s 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 ³IL 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鈥搊rganic PDT as an alternate treatment strategy for challenging environments such as malignant melanoma.