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

Manganese oxide nanoparticles (MnO 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 NPs (MnO, MnO, and MnO NPs) towards biologically relevant antioxidants (ascorbate and glutathione (GSH)) and reactive oxygen species (ROS) (hydrogen peroxide (HO), superoxide anion, and hydroxyl radical). We found that all three MnO 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 NPs in their catalytic activities towards different reactions. MnO shows the strongest ascorbate oxidation activity, followed by MnO and MnO, while MnO shows the strongest oxidation efficiency towards GSH compared to MnO and MnO. In the catalyzed decomposition of HO, MnO NPs show higher efficiency in the generation of molecular oxygen than MnO or MnO. Cellular studies indicate that all three MnO NPs induced concentration-dependent decreases in the cell viability, with MnO > MnO > MnO. At lower concentrations (<100 μM), consistent with the enzyme-like activities detected in solution, all three NPs significantly decreased HO-induced cytotoxicity in Caco-2 cells. Our study determined the multi-enzymatic activities of MnO NPs and exhibited differences among MnO 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 NPs as ROS-scavenging biomedical nanomaterials.