Protection of manganese oxide nanoparticles for bone marrow mesenchymal stem cell spreading against oxidative stress

doi:10.12307/2023.230

Abstract

Abstract: BACKGROUND: During stem cell transplantation, the generation of a large number of free radicals damages the cells in situ, and then reducing the cell survival. In the past decade, the emergence of nanozymes provides a new method for scavenging excess free radicals. Among them, manganese oxide (Mn3O4) is one of the promising nanomaterials, because it could provide Mn trace elements in human body as well as its well antioxidative stress properties and biodegradability. Mn3O4 can be used as a new type of nanomaterial to protect the extension function of stem cells.
OBJECTIVE: To produce Mn3O4 nanoparticles for detecting its effect on scavenging and spreading function of bone marrow mesenchymal stem cells during oxidative stress.
METHODS: Mn3O4 nanoparticles were prepared by hydrothermal method. Scanning electron microscope and X-ray diffraction were used to characterize the morphology and structure of Mn3O4, respectively. The particle size and zetapotential data of the nanoparticle in human-simulated environment were detected by the dynamic light scattering. The antioxidant capacity of Mn3O4 was tested in neutral environment. The CCK-8 and live-dead staining assays were utilized to verify the biological toxicity of Mn3O4 to bone marrow mesenchymal stem cells. H2O2 was used to induce oxidative stress of bone marrow mesenchymal stem cells. The effect of Mn3O4 on antioxidant ability and spreading ability of bone marrow mesenchymal stem cells was detected under oxidative stress.
RESULTS AND CONCLUSION: (1) The results of scanning electron microscope and X-ray diffraction exhibited that the material was Mn3O4 with average particle size about 70-80 nm. The dynamic light scattering showed that the particle size of the nanoparticles in PBS solution was about 100 nm, and the Zeta potential was about +20 mV. Antioxidant performance experiments showed that Mn3O4 had a certain antioxidant capacity. (2) The CCK-8 assay, live-death staining and reactive oxygen scavenging experiment demonstrated that Mn3O4 did not show biotoxicity and exhibited a certain level of reactive oxygen scavenging ability under 40 mg/L. (3) The cell spreading analysis showed that H2O2 had a significant inhibitory effect on the spreading function of bone marrow mesenchymal stem cells. After adding Mn3O4 into the cell culture microenvironment, the cell spreading area had no significant difference compared with the control group (P > 0.05). Moreover, the single use of Mn3O4 did not inhibit the spreading function of bone marrow mesenchymal stem cells (P > 0.05). (4) The results have shown that the addition of Mn3O4 nanoparticles in the cell microenvironment can resist oxidative stress and have a certain protective effect on the spreading function of bone marrow mesenchymal stem cells.

Key words: manganese oxide, nanoparticle, nanozyme, anti-oxidative stress, reactive oxygen species scavenging, stem cell transplantation, stem cell spreading, stem cell protection

CLC Number:

Tian Qinyu, Tian Xinggui, Tian Zhuang, Sui Xiang, Liu Shuyun, Lu Xiaobo, Guo Quanyi. Protection of manganese oxide nanoparticles for bone marrow mesenchymal stem cell spreading against oxidative stress[J]. Chinese Journal of Tissue Engineering Research, 2023, 27(6): 821-826.

Figures/Tables 6

References

[1] NATHAN C, CUNNINGHAM-BUSSEL A. Beyond oxidative stress: an immunologist’s guide to reactive oxygen species. Nat Rev Immunol. 2013; 13(5):349-361.
[2] FINKEL T, HOLBROOK NJ. Oxidants, oxidative stress and the biology of ageing. Nature. 2000;408(6809):239-247.
[3] GHORBANI M, DERAKHSHANKHAH H, JAFARI S, et al. Nanozyme antioxidants as emerging alternatives for natural antioxidants: Achievements and challenges in perspective. Nano Today. 2019;29:100775-100781.
[4] IMLAY JA, LINN S. DNA damage and oxygen radical toxicity. Science. 1988; 240(4857):1302-1309.
[5] YANG B, CHEN Y, SHI J. Reactive Oxygen Species (ROS)-Based Nanomedicine. Chem Rev. 2019;119(8):4881-4985.
[6] VALLE-PRIETO A, CONGET PA. Human mesenchymal stem cells efficiently manage oxidative stress. Stem Cells Dev. 2010;19(12):1885-1893.
[7] ZVIBEL I, SMETS F, SORIANO H. Anoikis: roadblock to cell transplantation? Cell Transplant. 2002;11(7):621-630.
[8] MATHIEU PS, LOBOA EG. Cytoskeletal and focal adhesion influences on mesenchymal stem cell shape, mechanical properties, and differentiation down osteogenic, adipogenic, and chondrogenic pathways. Tissue Eng Part B Rev. 2012;18(6):436-444.
[9] DENU RA, HEMATTI P. Effects of Oxidative Stress on Mesenchymal Stem Cell Biology. Oxid Med Cell Longev. 2016;2016:2989076.
[10] SONG H, CHA MJ, SONG BW, et al. Reactive oxygen species inhibit adhesion of mesenchymal stem cells implanted into ischemic myocardium via interference of focal adhesion complex. Stem Cells. 2010;28(3):555-563.
[11] FRAISL P, ARAGONÉS J, CARMELIET P. Inhibition of oxygen sensors as a therapeutic strategy for ischaemic and inflammatory disease. Nat Rev Drug Discov. 2009;8(2):139-152.
[12] WU J, WANG X, WANG Q, et al. Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes (II). Chem Soc Rev. 2019;48(4):1004-1076.
[13] WANG L, ZHU B, DENG Y, et al. Biocatalytic and Antioxidant Nanostructures for ROS Scavenging and Biotherapeutics. Adv Funct Mater. 2021;31(31): 2170226.
[14] HUANG Y, REN J, QU X. Nanozymes: Classification, Catalytic Mechanisms, Activity Regulation, and Applications. Chem Rev. 2019;119(6):4357-4412.
[15] JI S, JIANG B, HAO H, et al. Matching the kinetics of natural enzymes with a single-atom iron nanozyme. Nature Catalysis. 2021;4(5):407-417.
[16] JIANG D, NI D, ROSENKRANS ZT, et al. Nanozyme: new horizons for responsive biomedical applications. Chem Soc Rev. 2019;48(14):3683-3704.
[17] YANG W, YANG X, ZHU L, et al. Nanozymes: Activity origin, catalytic mechanism, and biological application. Coordination Chemistry Reviews. 2021;448:214170.
[18] HUANG G, ZANG J, HE L, et al. Bioactive Nanoenzyme Reverses Oxidative Damage and Endoplasmic Reticulum Stress in Neurons under Ischemic Stroke. ACS Nano. 2021;16(1):431-452.
[19] SHI J, YU W, XU L, et al. Bioinspired Nanosponge for Salvaging Ischemic Stroke via Free Radical Scavenging and Self-Adapted Oxygen Regulating. Nano Lett. 2020;20(1):780-789.
[20] JIANG X, GRAY P, PATEL M, et al. Crossover between anti- and pro-oxidant activities of different manganese oxide nanoparticles and their biological implications. J Mater Chem B. 2020;8(6):1191-1201.
[21] ZHANG S, LI H, WU Z, et al. Effects of Co doping on the structure and physicochemical properties of hausmannite (Mn3O4) and its transformation during aging. Chemical Geology. 2021;582:120448.
[22] CHENG Y, CHENG C, YAO J, et al. Mn3O4 Nanozyme for Inflammatory Bowel Disease Therapy. Advanced Therapeutics. 2021; 4(9):2100081-2100090.
[23] DING B, ZHENG P, MA P, et al. Manganese Oxide Nanomaterials: Synthesis, Properties, and Theranostic Applications. Adv Mater. 2020;32(10):e1905823.
[24] QIAN X, HAN X, YU L, et al. Manganese‐Based Functional Nanoplatforms: Nanosynthetic Construction, Physiochemical Property, and Theranostic Applicability. Adv Funct Mater. 2019;30(3):1907066.
[25] HAN SI, LEE SW, CHO MG, et al. Epitaxially Strained CeO2/Mn3O4 Nanocrystals as an Enhanced Antioxidant for Radioprotection. Adv Mater. 2020;32(31):2001566.
[26] TAYLOR KM, RIETER WJ, LIN W. Manganese-based nanoscale metal-organic frameworks for magnetic resonance imaging. J Am Chem Soc. 2008;130(44): 14358-14359.
[27] YAO J, CHENG Y, ZHOU M, et al. ROS scavenging Mn3O4 nanozymes for in vivo anti-inflammation. Chem Sci. 2018;9(11):2927-2933.
[28] WANG Y, CAI R, CHEN C. The Nano-Bio Interactions of Nanomedicines: Understanding the Biochemical Driving Forces and Redox Reactions. Acc Chem Res. 2019;52(6):1507-1518.
[29] DING J, YAO Y, LI J, et al. A Reactive Oxygen Species Scavenging and O2 Generating Injectable Hydrogel for Myocardial Infarction Treatment In vivo. Small. 2020;16(48):e2005038.
[30] TANG Z, ZHAO P, WANG H, et al. Biomedicine Meets Fenton Chemistry. Chem Rev. 2021;121(4):1981-2019.
[31] VARSOU DD, AFANTITIS A, TSOUMANIS A, et al. Zeta-Potential Read-Across Model Utilizing Nanodescriptors Extracted via the NanoXtract Image Analysis Tool Available on the Enalos Nanoinformatics Cloud Platform. Small. 2020;16(21):e1906588.
[32] PREMA P, NGUYEN VH, VENKATACHALAM K, et al. Hexavalent chromium removal from aqueous solutions using biogenic iron nanoparticles: Kinetics and equilibrium study. Environ Res. 2022;205:112477.
[33] ABDEL-RASHID RS, HELAL DA, ALAA-ELDIN AA, et al. Polymeric versus lipid nanocapsules for miconazole nitrate enhanced topical delivery: in vitro and ex vivo evaluation. Drug Deliv. 2022;29(1):294-304.
[34] XU Z, QU A, WANG W, et al. Facet-Dependent Biodegradable Mn3O4 Nanoparticles for Ameliorating Parkinson’s Disease. Adv Healthc Mater. 2021;10(23):e2101316.
[35] BARATI S, MOVAHEDIN M. The Antioxidant Effects of Calligonum Extract on Oxidative Stress in Spermatogonial Stem Cells Culture. Pharmaceutical Sciences. 2021;27(4):521-527.
[36] IM GB, KIM YG, JO IS, et al. Effect of polystyrene nanoplastics and their degraded forms on stem cell fate. J Hazard Mater. 2022;430:128411.
[37] SHOU JW, LI XX, TANG YS, et al. Novel mechanistic insight on the neuroprotective effect of berberine: The role of PPARδ for antioxidant action. Free Radic Biol Med. 2022;181:62-71.
[38] KURIAN AG, SINGH RK, LEE JH, et al. Surface-Engineered Hybrid Gelatin Methacryloyl with Nanoceria as Reactive Oxygen Species Responsive Matrixes for Bone Therapeutics. ACS Appl Bio Mater. 2022 Feb 22. doi: 10.1021/acsabm.1c01189.
[39] LEE S, LEE J, BYUN H, et al. Evaluation of the anti-oxidative and ROS scavenging properties of biomaterials coated with epigallocatechin gallate for tissue engineering. Acta Biomater. 2021;124:166-178.
[40] HEMACHANDRA LP, SHIN DH, DIER U, et al. Mitochondrial Superoxide Dismutase Has a Protumorigenic Role in Ovarian Clear Cell Carcinoma. Cancer Res. 2015;75(22):4973-4984.
[41] LIU YQ, MAO Y, XU E, et al. Nanozyme scavenging ROS for prevention of pathologic alpha-synuclein transmission in Parkinson’s disease. Nano Today. 2021;36:101027.
[42] ZELLER KS, RIAZ A, SARVE H, et al. The role of mechanical force and ROS in integrin-dependent signals. PLoS One. 2013;8(5):e64897.
[43] KANG DH, KANG SW. Targeting cellular antioxidant enzymes for treating atherosclerotic vascular disease. Biomol Ther (Seoul). 2013;21(2):89-96.