A long-lived cuprous bis-phenanthroline complex for the photodynamic therapy of cancer.

Abstract

Copper is an earth-abundant and a biologically essential metal that offers a promising alternative to noble metals in photochemistry and photobiology. In this work, a series of sterically encumbered Cu(i) bis-phenanthroline complexes were investigated for their use in photochemotherapy (PCT). It was found that Cu(dsbtmp)2+ [dsbtmp = 2,9-disec-butyl-3,4,7,8-tetramethyl-1,10-phenanthroline] (compound 3), which possessed the longest excited state lifetime, exhibited significant in vitro photocytotoxicity on A375 (human malignant melanoma) and A549 (human lung carcinoma) cell lines. Fluorescence imaging demonstrated the significant uptake and localization of compound 3 in a perinuclear fashion. A comet assay indicated the induction of DNA damage in the dark. The DNA breaks were significantly amplified upon photoactivation. The light-induced enhancement of cytotoxicity was associated with the formation of reactive oxygen species (ROS), a known intermediate in photodynamic therapy (PDT). This successful demonstration of photocytotoxicity using long-lived cuprous phenanthroline paves the way to exploit this class of photosensitizers for PDT applications.

• Authors: Cynthia Al Hageh, Majd Al Assaad, Zeinab El Masri, Nawar Samaan, Mirvat El-Sibai, Christian Khalil, Rony S Khnayzer
• Journal: Dalton transactions (Cambridge, England : 2003) (Dalton Trans) Vol. 47 Issue 14 Pg. 4959-4967 (Apr 03 2018) ISSN: 1477-9234 [Electronic] England
• PMID: 29557474 (Publication Type: Journal Article)

Chemical References

• Coordination Complexes
• Phenanthrolines
• Photosensitizing Agents
• Reactive Oxygen Species
• Copper

Topics

• A549 Cells
• Absorption, Physicochemical
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Coordination Complexes (chemical synthesis, chemistry, pharmacology)
• Copper (chemistry)
• DNA Damage (drug effects)
• Humans
• Phenanthrolines (chemistry)
• Photochemotherapy (methods)
• Photosensitizing Agents (chemical synthesis, chemistry, pharmacology)
• Reactive Oxygen Species