Crossover between anti- and pro-oxidant activities of different manganese oxide nanoparticles and their biological implications

Manganese oxide nanoparticles (MnO_x NPs) have been suggested to possess several enzyme-like activities. However, studies often used either color change or fluorescence to determine the catalytic activity. Despite the simplicity and sensitivity of these probes, these methods may give distracting artifacts or not reflect the catalytic activities in biological systems. To address this issue, herein, we used electron spin resonance (ESR) spectroscopy, a technique proven effective in identifying and quantifying the free radicals produced/scavenged in nanomaterial-catalyzed reactions, to systematically evaluate the catalytic activities of three MnO_x NPs (MnO₂, Mn₂O₃, and Mn₃O₄ NPs) towards biologically relevant antioxidants (ascorbate and glutathione (GSH)) and reactive oxygen species (ROS) (hydrogen peroxide (H₂O₂), superoxide anion, and hydroxyl radical). We found that all three MnO_x NPs possess both pro- and anti-oxidant activities, including oxidase-, catalase-, and superoxide dismutase (SOD)-like activities but without peroxidase-like or hydroxyl radical scavenging activity. In addition, there are differences among these MnO_x NPs in their catalytic activities towards different reactions. Mn₂O₃ shows the strongest ascorbate oxidation activity, followed by MnO₂ and Mn₃O₄, while Mn₃O₄ shows the strongest oxidation efficiency towards GSH compared to Mn₂O₃ and MnO₂. In the catalyzed decomposition of H₂O₂, MnO₂ NPs show higher efficiency in the generation of molecular oxygen than Mn₂O₃ or Mn₃O₄. Cellular studies indicate that all three MnO_x NPs induced concentration-dependent decreases in the cell viability, with Mn₃O₄ > Mn₃O₂ > MnO₂. At lower concentrations (<100 μM), consistent with the enzyme-like activities detected in solution, all three NPs significantly decreased H₂O₂-induced cytotoxicity in Caco-2 cells. Our study determined the multi-enzymatic activities of MnO_x NPs and exhibited differences among MnO_x NPs of different valences in their enzyme-like activities and their biological implications; these results provide valuable information for safe and efficient applications of MnO_x NPs as ROS-scavenging biomedical nanomaterials.