Influence of redox cyclers on thiol oxidation in the presence of nanoparticles

Background: An increase in metabolic rate interconnected with oxidative imbalance are major features of tumor process. Higher ROS (reactive oxygen species) levels make tumor cells more sensitive to oxidative stress compared to normal cells. Therefore, generating additional ROS can lead to cancer cell death. Redox cycling is a crucial process responsible for the production of ROS by various clinical and experimental anticancer agents. Among these compounds are quinones and ascorbic acid, which exhibits a synergistic antitumor effect. Elevated glutathione levels and glutathione-dependent antioxidant enzymes play a key role in protecting cancer cells from intracellular oxidative stress. Nanoparticles with glutathione depletion properties can act as smart chemodynamic agents, disrupting the cellular antioxidant defense system. In this work, inorganic nanoparticles based on rare earth elements are used as catalytic amplifiers of one- electron transfer with the formation of organic and oxygen radicals in the redox cycles of ascorbic acid and vitamin K3. Objectives: The thiol oxidation was studied in the presence of nanoparticles in combination with redox cyclers. Materials and methods: As an indicator of the pro-oxidant efficiency of nanoparticles (CeO2 (2 nm, 20 μg/ml) or GdYVO4:Eu3+ (2 nm, 20 μg/ml)) combined with organic compounds (ascorbic acid (100 or 200 µM) and vitamin K3 (4 μM)) changes in the level of thiols (glutathione (200 μM), L-cysteine (200 μM) or dithiothreitol (500 μM)) in the model system were used. Results: It was shown that GdYVO4:Eu3+ and CeO2 nanoparticles enhances oxidation of thiols under an influence of the redox active molecule as well as their combination. The efficiency of bare nanoceria as well as in redox cyclers combinations was higher compared to respective orthovanadate nanoparticles combinations (including time dynamics) that was especially pronounced in the dithiothreitol oxidation system. Conclusions: The data obtained indicate the ability of nanoceria to significantly enhance the oxidation of thiols induced by redox cyclers revealing the perspective of this approach in solving the problem of increased thiol level in tumor cells.