Poster Presentation 21st International Conference on Biological Inorganic Chemistry 2025

Photodynamically active Ir(III) and Ru(II) ethynyl Nile Red complexes for efficient cancer treatment (#538)

Amani B. Al Riyami 1 , Judit Fodor 1 , Claire Condon 1 , Olga Mazuryk 2 , Małgorzata Brindell 2 , Stephen O Sullivan 3 , Mary T. Pryce 3 , Sylvia M. Draper 1
  1. School of Chemistry, Trinity College Dublin, Dublin 2, Dublin, Ireland
  2. Department of Inorganic Chemistry, Faculty of Chemistry, Jagiellonian University, Krakow, Poland
  3. School of Chemical Sciences, Dublin City University, Dublin 9, Dublin, Ireland

Photodynamic Therapy (PDT) is a well-established yet relatively recent approach in cancer treatment that uses a non-toxic photosensitizer (PS) which when activated by light generates cytotoxic species that destroy cancer cells.1 Unlike chemotherapy, radiotherapy or immunotherapy PDT precisely targets specific tissue areas while leaving healthy, non-irradiated tissues undamaged. The key requirements of PDT agents include operating within the therapeutic window (630–960 nm), achieving a high singlet oxygen quantum yield (>30%), exhibiting low dark toxicity, strong bio- and photo-stability, rapid and selective cell death at low concentrations, and speedy excretion after treatment.1, 2 Iridium and ruthenium polypyridine complexes are very attractive for photobiological applications due to their strong absorption in the visual region, high stability, and long-lived excited states. These properties result from effective energy transfer between well-matched triplet excited states involving the metal centre and/or a conjugated ligand.3, 4

This work explores the synthesis, characterization, and biological applications of novel Iridium(III) and Ruthenium(II) complexes that incorporate the ethynyl Nile Red chromophore. It investigates their photophysical properties and excited state behaviour including altered absorption and emission wavelengths, emission lifetimes and quantum yields. The effectiveness of these compounds in PDT are tested through in vitro studies using a breast cancer cell line. Cytotoxicity results show that the asymmetric Ru(II) ethynyl Nile Red complex exhibits no cytotoxicity after 72 hours but dramatically increases its antiproliferative activity upon irradiation at 520 nm for 5 mins, (IC50hν = 290 nM). Reactive oxygen species (ROS) studies confirms exceptional levels of hydrogen peroxide (H2O2) and singlet oxygen (1O2) generation. Cellular uptake analyses under normoxic and hypoxic conditions reveal the effective accumulation of the novel Ru(II) ethynyl Nile Red complex within MCF-7 cells and high activity levels under the hypoxic conditions of most tumours.

 

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