Pre-clinical study of non-platinum metalodrugs for lung cancer therapy
Lung cancer is the malignant tumour disease, that is, together with breast cancer, the most diagnosed cancer type world-wide, with about 11% of 19 million of new patients. Importantly, lung cancer is the most frequent cause of death within all cancers, with ca. 2-fold higher portion than the second one (colorectal cancer). These facts, together with smoking as the most frequent cause of lung cancer (ca. 85–90 % incidence), implies that the development of new drugs is required for the lung cancer therapy. The project deals with the experimental development of new drugs and therapeutic formulations for the treatment of lung cancer. Anticancer activity will be studied in detail for organometallic compounds of selected metals (Ru, Rh, Ta, Os and Ir), which have been recently tested for their cytotoxicity (proof-of-concept for the project) or will be prepared within the project for the first time. An attention will be paid to the stability studies in various media (e.g. blood serum). Complexes will be tested in vitro at cancerous (including the resistant ones) and non-cancerous cell lines derived from the lung tissue. The activity of compounds with high selectivity towards the cancer cells will be studied in the pre-clinical model of lung cancer in mice. An effect of these compounds will be tuned by their formulation into liposomes aiming to improve their activity (by targeting to cancer cells) and reduce their negative side-effects. We expect, that the project will bring the original and innovative findings regarding the anticancer activity of new metallodrugs and their nanocarriers for targeted drug delivery. Two research teams will participate in the project. The Department of Inorganic Chemistry (Palacký University in Olomouc) is long-term focused on the research and development of new bioactive complexes, while the Department of Pharmacology and Toxicology (Veterinary Research Institute, Brno) deals with the supramolecular targeted therapeutics of various disease.