Targeted release of anticancer agents by acidic environment.
Ruthenium complexes possess potent cytotoxic activity. Therefore, the compounds of rare metals are discussed as an alternative to cisplatin in the treatment of tumor diseases. However, efficient systems for selective drug delivery to tumor tissue are still being sought. IPB chemists, together with partners from Merseburg, Munich and Serbia, have now worked on the construction of such a drug delivery system for cytotoxic Ru(II) complexes. It is based on binding of the ruthenium complexes to mesoporous silica nanoparticles. This fixation of the metal complexes to the nanoparticles’ surface was done by additional ligands, which were linked to the silica particle via a pH-dependent hydrazone bond. A slight decrease in pH led to the cleavage of the hydrazone bond and thus to the detachment of the ligand-Ru(II) complexes. The scientists demonstrated that the ligands coupled to the drug did not interfere with the cytotoxic activity of the ruthenium complex. The ruthenium-ligand complexes showed strong cytotoxic effects on melanoma cells in cell cultures. The potential mode of action of this drug delivery system in living organisms is based on the observation that malignant tissues are always slightly more acidic than surrounding tissues due to the enhanced lactic acid fermentation of cancer cells. This could enable a targeted release of the anticancer agents in the acidic environment of tumors.