Accumulating evidence suggests that manganese oxide nanoparticles (NPs) show multiple enzyme-mimicking antioxidant activities, which supports their potential in redox-targeting therapeutic strategies for diseases with impaired redox signaling. However, the systemic administration of any NP requires thorough hemocompatibility testing. In this study, we assessed the hemocompatibility of synthesized Mn3O4 NPs, identifying their ability to induce spontaneous hemolysis and eryptosis or impair osmotic fragility. Concentrations of up to 20 mg/L were found to be safe for erythrocytes. Eryptosis assays were shown to be more sensitive than hemolysis and osmotic fragility as markers of hemocompatibility for Mn3O4 NP testing. Flow cytometry- and confocal microscopy-based studies revealed that eryptosis induced by Mn3O4 NPs was accompanied by Ca2+ overload, altered redox homeostasis verified by enhanced intracellular reactive oxygen species (ROS) and reactive nitrogen species (RNS), and a decrease in the lipid order of cell membranes. Furthermore, Mn3O4 NP-induced eryptosis was calpain- and caspase-dependent.
- MeSH
- Cell Membrane * metabolism drug effects MeSH
- Eryptosis * drug effects MeSH
- Erythrocytes drug effects metabolism MeSH
- Hemolysis drug effects MeSH
- Calpain * metabolism MeSH
- Caspases * metabolism MeSH
- Humans MeSH
- Nanoparticles * chemistry MeSH
- Oxides * pharmacology chemistry MeSH
- Reactive Nitrogen Species * metabolism MeSH
- Reactive Oxygen Species * metabolism MeSH
- Manganese Compounds * pharmacology chemistry MeSH
- Calcium * metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
