Enhancement of Thiol Oxidation by Redox Cyclers in the Presence of Nanoparticles in Model System

Redox-cycling compounds, such as quinones and ascorbic acid, are widely used in tumor chemotherapy, often demonstrating a synergistic antitumor effect. In this study, inorganic nanoparticles (NPs) based on rare earth elements were employed as catalytic amplifiers to facilitate one-electron transfer, leading to the generation of organic and oxygen radicals in the redox cycles of ascorbic acid and vitamin K3. The pro-oxidant efficiency of NPs ($\mathrm{CeO}_{2}(2 \mathrm{~nm}, 20$ $\mu \mathrm{g} / \mathrm{ml})$ or GdYVO4Eu ${ }^{3+}(2 \mathrm{~nm}, 20 \mu \mathrm{~g} / \mathrm{ml})$) combined with organic compounds (ascorbic acid (100 or $200 \mu \mathrm{M}$), vitamin K 3 $(4 \mu \mathrm{M})$) was evaluated using changes in the levels of thiols—glutathione ($200 \mu \mathrm{M}$), L-cysteine ($200 {\mu {\mathrm {M}}}$), or dithiothreitol $(500 \mu \mathrm{M})$ —in a model system. The study examined the pH dependence ($\mathrm{pH} 6.7,7.4,7.8$) and time dynamics of the process over a 24-hour period. Results revealed that the presence of orthovanadate and cerium dioxide NPs significantly enhanced the oxidation of thiols in response to each redox-cycler and their combination. Nanoceria exhibited a higher efficiency compared to orthovanadate NPs, particularly in the dithiothreitol oxidation system, including the observed time dynamics. These findings highlight the potential of nanoceria to markedly enhance thiol oxidation induced by redox cyclers, suggesting a promising approach to address elevated thiol levels in tumor cells.