Photodynamic therapy is method of cancer treatment which utilises photosensitisers to generate reactive oxygen species, inducing cell death1. Metal complexes with a d6 electronic configuration such as iridium (III) and ruthenium (II) are well suited for use in photodynamic therapy due to their long luminescent lifetimes and large stokes shifts, allowing for excitation with visible light2. Four luminescent metal complexes were synthesised using either 2-pyridin-2-yl-quinoline-4-carboxylic acid (pyquin) or bicinchoninic acid (BCA) as bidentate ligands. Both pyquin and BCA contain carboxylic acid functional groups which have the potential to allow for future incorporation of biomolecules such as antibodies and peptides for cellular targeting3. All four complexes were found to emit red to near-infrared light and produce 1O2, which is critical for potential applications in photodynamic therapy as it is a key reactive oxygen species for causing cell death.
The pyquin-iridium (III) complex was modified with a polyethylene linker squaramide functional group to improve its aqueous solubility and to allow for the attachment of proteins and antibodies via reaction with a lysine residue above pH 94. The squaramide complex was then conjugated to Herceptin and transferrin for targeting of human epidermal growth factor receptor 2 (HER2) and transferrin receptor (TfR) positive cells. Both of these receptors are overexpressed in a wide variety of cancer types such as breast, bladder and lung cancers5,6. Both iridium (III) metal conjugates were imaged using confocal microscopy in SKOV-3 cells which overexpress both HER2 and TfR to visualise their cellular uptake. These metal complexes present an alternative to traditional fluorophores for cellular sensing and potentially as photodynamic therapy agents, depending on their cytotoxicity.
(1) Przygoda, M.; Bartusik-Aebisher, D.; Dynarowicz, K.; Cieślar, G.; Kawczyk-Krupka, A.; Aebisher, D. Cellular Mechanisms of Singlet Oxygen in Photodynamic Therapy. Int J Mol Sci 2023, 24 (23), 16890. https://doi.org/10.3390/ijms242316890.
(2) Connell, T. U.; James, Janine. L.; White, A. R.; Donnelly, P. S. Protein Labelling with Versatile Phosphorescent Metal Complexes for Live Cell Luminescence Imaging. Chemistry – A European Journal 2015, 21 (40), 14146–14155. https://doi.org/10.1002/chem.201501630.
(3) Kimchi, L.; McGowan, E. R.; Morgan, K. A.; White, J. M.; Smith, T. A.; Rudd, S. E.; Donnelly, P. S. Phosphorescent Iridium Hydrazinonicotinic Acid (HYNIC) Complexes That Bind to Prostate Specific Membrane Antigen: Potential Photodynamic Therapy of Prostate Cancer. Chemistry – A European Journal 2026, n/a (n/a), e71011. https://doi.org/10.1002/chem.71011.
(4) Rudd, S. E.; Roselt, P.; Cullinane, C.; Hicks, R. J.; Donnelly, P. S. A Desferrioxamine B Squaramide Ester for the Incorporation of Zirconium-89 into Antibodies. Chem. Commun. 2016, 52 (80), 11889–11892. https://doi.org/10.1039/C6CC05961A.
(5) Prior, R.; Reifenberger, G.; Wechsler, W. Transferrin Receptor Expression in Tumours of the Human Nervous System: Relation to Tumour Type, Grading and Tumour Growth Fraction. Vichows Archiv A Pathol Anat 1990, 416 (6), 491–496. https://doi.org/10.1007/BF01600299.
(6) Iqbal, N.; Iqbal, N. Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications. Mol Biol Int 2014, 2014, 852748. https://doi.org/10.1155/2014/852748.