Abstract:

Despite many excellent medical achievements in the field of cancer therapies, resistance to chemotherapy as well as disease relapses remain a huge clinical challenge. One of the strategies in designing new anticancer therapeutics is the use of compounds based on metal ions surrounded by selected ligands (metal drugs). Different metal centers may exhibit different coordination geometries and redox capabilities, while ligands may additionally exhibit different biological activities. Moreover, metal ions have a high affinity for biologically important intracellular thiols, which may significantly disturb the intracellular redox balance, lead to protein and enzyme dysfunction, and even to the accumulation of lipid peroxides inside the cell, which may result in cell death via the so-called ferroptosis.

The main objectives of the presented project are the design, synthesis, and characterization of Ru(II), Ir(III), Os(II) mononuclear as well as heteronuclear Ru(II)/Cu(II), Ir(III)/Cu(II) complexes leading to ferroptosis of drug-resistant cancer cells. We tried to better understand the stability and behavior of the proposed compounds in biological systems (cells, spheroids, zebrafish model, fig. 1), and their interaction with high and low molecular biomolecules (e.g., ctDNA, plasmid DNA, 9-ethylguanine, 9-methyladenin, human albumins, nicotinamide adenine dinucleotide, cysteine, glutathione, and ascorbic acid) mimicking natural, biological environment. In addition, to improve the efficiency and reliability of drug delivery to the tumor site, nanoparticle systems for drug delivery (e.g., liposome, bilosomes, micelle, magnetic micelle) have been developed.

Speaker Bio:

Dr hab. Urszula K. Komarnicka is an Associate Professor from Poland, affiliated with the Department of Biological and Medicinal Chemistry at the University of Wrocław where She received her PhD in Inorganic Chemistry in 2016. Her research focuses on medicinal inorganic chemistry, especially organometallic phosphine complexes, their anticancer mechanisms (including ferroptosis induction), and their interactions with biomolecules.

Her international scientific experience includes several postdoctoral stays in Italy: at ICMATE – Institute of Condensed Matter Chemistry and Energy Technologies in Padova, where she worked on phosphine ligands and copper(I) complexes, and at the Department of Pharmaceutical and Pharmacological Sciences, University of Padova, where she focused on biological assays and cell culture studies. She subsequently undertook a research stay at Colorado State University (USA) working on phosphino-vanadium complexes and completed additional research work at Palacký University Olomouc (Czech Republic).

Dr. Komarnicka leads competitive NCN and NAWA-funded research projects, collaborates internationally, and has authored numerous publications in high-impact journals. She serves on editorial boards such as Frontiers in Chemical Biology, Pharmaceuticals, and the Early Career Board of Coordination Chemistry Reviews. She is also an experienced academic mentor who has supervised many bachelor’s, master’s, and PhD students, and is an active invited speaker at international conferences.