Mn3O4 Nanocrystal-Induced Eryptosis Features Ca2+ Overload, ROS and RNS Accumulation, Calpain Activation, Recruitment of Caspases, and Changes in the Lipid Order of Cell Membranes
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 Mn<sub>3</sub>O<sub>4</sub> 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 Mn<sub>3</sub>O<sub>4</sub> NP testing. Flow cytometry- and confocal microscopy-based studies revealed that eryptosis induced by Mn<sub>3</sub>O<sub>4</sub> NPs was accompanied by Ca<sup>2+</sup> 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, Mn<sub>3</sub>O<sub>4</sub> NP-induced eryptosis was calpain- and caspase-dependent.
Authors
- Vladimir Klochkov (ORCID: https://orcid.org/0000-0002-8080-1195)
- Lesya Demchenko (ORCID: https://orcid.org/0000-0002-2325-1940)
- Ondřej Havránek (ORCID: https://orcid.org/0000-0001-5826-3557)
- Yuriy Kot
- Volodymyr Prokopіuk (ORCID: https://orcid.org/0000-0003-4379-4130)
- Anatolii Onishchenko (ORCID: https://orcid.org/0000-0002-2122-2361)
- Pavel Maksimchuk (ORCID: https://orcid.org/0000-0001-5448-1274)
- Anton Tkachenko (ORCID: https://orcid.org/0000-0002-1029-1636)
- Andrey V. Aslanov (ORCID: https://orcid.org/0000-0002-2754-1355)
- Liliya Tryfonyuk (ORCID: https://orcid.org/0000-0003-0307-3048)
- Svetlana Yefimova (ORCID: https://orcid.org/0000-0003-2092-1950)
- Kateryna Kot (ORCID: https://orcid.org/0000-0003-4814-847X)
- Oleg Avrunin
- Saulesh Kurmangaliyeva
Institutions
- Kharkiv National University of Radio Electronics (UA)
- National Academy of Sciences of Ukraine (UA)
- Stockholm University (SE)
- National Technical University of Ukraine “Igor Sikorsky Kyiv Polytechnic Institute” (UA)
- Charles University (CZ)
- National University of Water and Environmental Engineering (UA)
- West Kazakhstan Marat Ospanov State Medical University (KZ)
- Institute for Scintillation Materials (UA)
- Institute for Problems of Cryobiology and Cryomedicine (UA)
- Kharkiv National Medical University (UA)
- V. N. Karazin Kharkiv National University (UA)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2025-04-01
- DOI
- https://doi.org/10.3390/ijms26073284
- Citations
- 2
- Primary Topic
- Erythrocyte Function and Pathophysiology
- Type
- article
- Field-Weighted Citation Impact
- 2.33
Funders
- European Hematology Association
- Ministerstvo Školství, Mládeže a Tělovýchovy