Ruthenium nitroimidazole conjugate as a theranostic agent for hypoxic tissue

Taking advantages of the luminescent properties of ruthenium polypyridyl complexes, further functionalization of ligands can increase the selectivity of such compound and create agents both for therapy and optical imaging. Ru polypyridyl complex with the attached nitroimidazole moiety was designed as a prospective hypoxia marker, so the evaluation of its selectivity upon oxygen-deprived conditions as well as cytotoxicity and mechanism of cellular death were investigated. Cytotoxicity of the studied Ru complex is superior to clinically used cisplatin. Additionally, it is more toxic towards cells expressing nitroreductase kept at hypoxia, than cultured under normoxia conditions. It has a longer retention time and higher accumulation in the cells growing under hypoxic conditions. These factors combined with the higher quantum yield and the larger luminescence lifetime measured in deoxygenated solutions, are good indicators to consider this complex for detection of the hypoxic tissues inside the body. Despise accumulation in mitochondria Ru-nitroimidazole conjugate leads neither to mitochondrial disfunction nor mitochondria-mediated apoptosis. Dramatic ROS production induced by the complex in vitro disrupts intracellular calcium homeostasis causing caspase-independent apoptosis.