Exposure of Prooxidant Potential of CeO2 and GdYVO4/Eu³⁺ Nanoparticles in Model Systems Containing Low-Molecular Antioxidants

Nanotechnology-based pro-oxidant strategy is perspective for cancer therapy. For instance, pro-oxidant properties of cerium oxide nanoparticles (nanpceria) observed under certain conditions, as well as its antitumor effect, have drawn a lot of attention in recent years. Thus, the aim of the study is to compare the pro-oxidant potential of CeO 2 and GdYVO4/Eu3+ nanoparticles (NPs) as the promoters of ROS-mediated antitumor activity. Extra-small 2 nm CeO 2 NPs or 2 nm GdYVO4/Eu3+ NPs were used in this research. The oxidation of ascorbic acid (AA), NADPH, and GSH molecules was monitored by spectroscopic methods at pH 6.7, 7.4, and 7.8. The solutions of NPs (with final concentrations of $\mathbf{10}-\mathbf{40}\ \boldsymbol{\mu} \mathbf{g}/\mathbf{mL}$ ) were added to organic (20 mM Tris or Hepes) buffers contained $\mathbf{200}\ \boldsymbol{\mu} \mathbf{mol}$ AA or $\mathbf{200}\ \boldsymbol{\mu} \mathbf{mol}$ NADPH or $\mathbf{50} \boldsymbol{\mu} \mathbf{mol}$ GSH. The mixture was kept for 60 min or 3 h, or 24 h at 37 °C, respectively. The AA oxidative damage was quantified by measuring its absorbance at the characteristic wavelengths $\boldsymbol{\lambda}\ \mathbf{max}=\mathbf{265}\ \mathbf{nm}$ (AA), 340 nm (NADPH), and 412 nm (GSH, after reaction with Elman reagent) using Specord 200 spectrophotometer (Analytik Jena, Germany). The literature reports on the potential antitumor activity of rare earth elements (REE) and REE-based nanoparticles, and in particular, of CeO 2 NPs and their combinations with antitumor agents. Data on the antitumor activity of GdYVO4/Eu3+ nanoparticles were also obtained. The pro-oxidant potential of nanoceria and, in particular, the ability to exhibit oxidizing activity under certain conditions with oxidation of organic substrates is discussed. We have carried out a comparative analysis of the oxidation of the most important low-molecular components of the antioxidant defense system in cells - AA, NADPH, and GSH in the presence of CeO 2 and GdYVO4/Eu3+ NPs. Oxidation of all studied compounds in the presence of CeO 2 NPs was shown. A drop in the level of AA compared with the control was noticed at all studied concentrations of nanoparticles and pH values. At the same time, CeO 2 NPs accelerated the oxidation of NADPH and glutathione only at neutral pH values. Unlike CeO2, GdYVO4/Eu3+ NPs decrease GSH level only under weakly alkaline conditions at NPs concentration of $\mathbf{10}\ \boldsymbol{\mu}\mathbf{g}/\mathbf{mL}$ and more. It was noted that the oxidation of GSH at pH 7.8 is accompanied by irreversible agglomeration of nanoparticles. Thus, under certain conditions, extra-small CeO 2 NPs demonstrate a significant pro-oxidant activity. This may create prerequisites for further aggravation of the redox imbalance against the background of constant oxidative stress of tumor cells and, as a result, more pronounced oxidative damage.