Cell and Tissue Biology

, 5:388 | Cite as

Effect of magnetic nanoparticles Fe3O4 on viability, attachment, and spreading of isolated fetuses and newborn rats

  • A. N. Sukach
  • A. S. Lebedinskii
  • V. I. Grishchenko
  • T. D. Lyashenko


This study has shown that the toxic effect of nonmodified Fe3O4 nanoparticles in vitro depends on the metabolic and morphological conditions of cells from rat fetuses and newborns. In the process of cultivation, cells with magnetic nanoparticles bind to their surface and penetrate the intracellular space. The sorption of nanoparticles on the cell surface hinders their attachment to the substrate and absorption by spread cells can prevent their proliferation. Magnetic nanoparticles are well sorbed by the upper layer of cell aggregates, whereas cells of the inner layer remain intact. As a result, the cell aggregates acquire the property of responding to a constant magnetic field. These aggregates could potentially be used in cell transplantation for directed cell delivery.


isolated cells cultivation magnetic nanoparticles lipid peroxidation toxicity 

Abbreviations used


newborn rat liver cell


rat fetal liver cell


malone dialdehyde


newborn rat neural cell


rat fetal neural cell


ferromagnetic Fe3O4 nanoparticle


thiobarbituric acid


rat fetal fibroblast


  1. Absolom, D.R., Zingg, W., and Neumann, A.W., Protein Adsorption to Polymer Particles: Role of Surface Properties, J. Biomed. Mater. Res., 1987, vol. 21, pp. 161–171.PubMedCrossRefGoogle Scholar
  2. Abts, H., Emmerich, M., Miltenyi, S., Radbruch, A., and Tesch, H., CD20 Positive Human B Lymphocytes Separated with the Magnetic Cell Sorter (MACS) Can Be Induced to Proliferation and Antibody Secretion in vitro, J. Immunol. Methods., 1989, vol. 125, pp. 19–28.PubMedCrossRefGoogle Scholar
  3. Andreeva, L.N., Modification of the Method for Determining Lipid Peroxides in the Test with Thiobarbituric Acid, Lab. Delo, 1988, vol. 11, pp. 41–43.PubMedGoogle Scholar
  4. Bareford, L.M. and Swaan, P.W., Endocytic Mechanisms for Targeted Drug Delivery, Adv. Drug Deliv. Rev., 2007, vol. 59, pp. 48–758.CrossRefGoogle Scholar
  5. Berry, C.C. and Curtis, A.S.G., Functionalisation of Magnetic Nanoparticles for Applications in Biomedicine, J. Phys. D. Appl. Phys., 2003, vol. 36, pp. 198–206.CrossRefGoogle Scholar
  6. Bhattarai, S.R., Kc, R.B., Kim, S.Y., Sharma, M., Khil, M.S., Hwang, P.H., Chung, G.H., and Kim, H.Y., N-Hexanoyl Chitosan Stabilized Magnetic Nanoparticles: Implication-for Cellular Labeling and Magnetic Resonance Imaging, J. Nanobiotech., 2008, vol. 6, pp. 1–9.CrossRefGoogle Scholar
  7. Brunner, T., Wick, P., Manser, P., Spohn, P., Grass, R., Limbach, L., Bruinink, A., and Stark, W., In Vitro Cytotoxicity of Oxide Nanoparticles: Comparison to Asbestos, Silica, and the Effect of Particle Solubility, Environ. Sci. Technol., 2006, vol. 40, pp. 4374–4381.PubMedCrossRefGoogle Scholar
  8. Cheng, F.Y., Su, C.H., Yang, Y.S., Yeh, C.S., Tsai, C.Y., Wu, C.L., Wu, M.T., and Shieh, D.B., Characterization of Aqueous Dispersions of Fe3O4 Nanoparticles and Their Biomedical Applications, Biomaterials, 2005, vol. 26, pp. 729–738.PubMedCrossRefGoogle Scholar
  9. Clement, J.H., Schwalbe, M., Buske, N., Wagner, K., Schnabelrauch, M., Gornert, P., Kliche, K.O., Pachmann, K., Weitschies, W., and Hoffken, K., Differential Interaction of Magnetic Nanoparticles with Tumor Cells and Peripheral Blood Cells, J. Cancer Res. Clin. Oncol., 2006, vol. 132, pp. 287–292.PubMedCrossRefGoogle Scholar
  10. Dewar, H., Warren, D.T., Gardiner, F.C., Gourlay, C.G., Satish, N., Richardson, M.R., Andrews, P.D., and Ayscough, K.R., Novel Proteins Linking the Actin Cytoskeleton to the Endocytic Machinery in Saccharomyces cerevisiae, Mol. Biol. Cell., 2002, vol. 13, pp. 3646–3661.PubMedCrossRefGoogle Scholar
  11. Gupta, A.K. and Curtis, A.S.G., Lactoferrin and Ceruloplasmin Derivatized Superparamagnetic Iron Oxide Nanoparticles for Targeting Cell Surface Receptors, Biomaterials, 2004, vol. 25, pp. 3029–3040.PubMedCrossRefGoogle Scholar
  12. Gupta, A.K. and Gupta, M., Cytotoxicity Suppression and Cellular Uptake Enhancement of Surface Modified Magnetic Nanoparticles, Biomaterials, 2005, vol. 26, pp. 1565–1573.PubMedCrossRefGoogle Scholar
  13. Gupta, A.K., Gupta, M., Yarwood, S.J., and Curtis, A.S.G., Effect of Cellular Uptake of Gelatin Nanoparticles on Adhesion, Morphology and Cytoskeleton Organisation of Human Fibroblasts, J. Control. Rel., 2004, vol. 95, pp. 197–207.CrossRefGoogle Scholar
  14. Guzman, R., Uchida, N., Bliss, T.M., He, D., Christopherson, K.K., Stellwagen, D., Capela, A., Greve, J., Malenka, R.C., Moseley, M.E., Palmer, T. D., and Steinberg, G.K., Long-term Monitoring of Transplanted Human Neural Stem Cells in Developmental and Pathological Contexts with MRI, Proc. Natl. Akad. Sci. USA, 2007, vol. 104, pp. 10211–10216.CrossRefGoogle Scholar
  15. Haas, T.A. and Plow, E.F., Integrin-Ligand Interactions: A Year in Review, Curr. Opin. Cell Biol., 1994, vol. 6, pp. 656–662.PubMedCrossRefGoogle Scholar
  16. Hussain, S.M., Hess, K.L., Gearhart, J.M., Geiss, K.T., and Schlager, J.J., In Vitro Toxicity of Nanoparticles in BRL 3A Rat Liver Cells, Toxicology in Vitro, 2005, vol. 19, pp. 975–983.PubMedCrossRefGoogle Scholar
  17. Ito, A., Hayashida, M., Honda, H., Hata, K., Kagami, H., Ueda, M., and Kobayashi, T., Construction and Harvest of Multilayered Keratinocyte Sheets using Magnetite Nanoparticles and Magnetic Force, Tissue Eng., 2004, vol. 10, pp. 873–880.PubMedCrossRefGoogle Scholar
  18. Ito, A., Hibino, E., Kobayashi, C., Terasaki, H., Kagami, H., Ueda, M., Kobayashi, T., Honda, and H., Construction and Delivery of Tissue Engineered Human Retinal Pigment Epithelial Cell Sheets, using Magnetite Nanoparticles and Magnetic Force, Tissue Eng., 2005, vol. 11, pp. 489–496.PubMedCrossRefGoogle Scholar
  19. Ito, A., Takizawa, Y., Honda, H., Hata, K., Kagami, H., Ueda, M., and Kobayashi, T., Tissue Engineering using Magnetite Nanoparticles and Magnetic Force: Heterotypic Layers of Cocultured Hepatocytes and Endothelial Cells, Tissue Eng., 2004, vol. 10, pp. 833–840.PubMedCrossRefGoogle Scholar
  20. Kim, J.S., Yoon, T.J., Yu, K.N., Noh, M.S., Woo, M., Kim, B.G., Lee, K.H., Sohn, B.H., Park, S.B., Lee, J.K., and Cho, M.H., Cellular Uptake of Magnetic Nanoparticle Is Mediated Through Energy-Dependent Endocytosis in A549 Cells, J. Vet. Sci., 2006, vol. 7, pp. 321–326.PubMedCrossRefGoogle Scholar
  21. Lyashenko, T.D. and Sukach, A.N., Characterization of Isolated Nerve Cells of Newborn Rats, Patologiya, 2009, vol. 6, no. 1, pp. 55–58.Google Scholar
  22. Lyman, S., Gilmore, A., Burridge, K., and Gidwitz, S., and White, G.C., 2nd Integrin-Mediated Activation of Focal Adhesion Kinase Is Independent of Focal Adhesion Formation or Integrin Activation. Studies with Activated and Inhibitory Beta 3 Cytoplasmic Domain Mutants, J. Biol. Chem., 1997, vol. 272, pp. 22538–22547.PubMedCrossRefGoogle Scholar
  23. Miltenyi, S., Muller, W., Weichel, W., and Radbruch, A., High Gradient Magnetic Cell Separation with MACS, Cytometry, 1990, vol. 11, pp. 231–238.PubMedCrossRefGoogle Scholar
  24. Molday, R.S. and MacKenzie, D., Immunospecific Ferromagnetic Iron Dextran Reagents for the Labeling and Magnetic Separation of Cells, J. Immunol. Methods, 1982, vol. 52, pp. 353–367.PubMedCrossRefGoogle Scholar
  25. Mondalek, F.G., Zhang, Y.Y., Kropp, B., Kopke, R.D., Ge, X., Jackson, R.L., and Dormer, K.J., The Permeability of SPION over an Artificial Three-layer Membrane Is Enhanced by External Magnetic Field, J. Nanobiotechnol., 2006, vol. 4, pp. 1–9.CrossRefGoogle Scholar
  26. Movchan, B.A., Electron Beam Nanotechnology and New Materials in Medicine — First Steps, Vestn. Farmakol. Farmats., 2007, vol. 12, pp. 5–13.Google Scholar
  27. Movchan, B.A., Kurapov, Yu.A., and Romanenko, S.M., Magnetic Fluid, Obtained by Electron Beam Evaporation and Condensation of Fe3O4 in a Vacuum, in Proc. Int. Conf. HighMatTech”, Kiev, 2007.Google Scholar
  28. Phanapavudhikul, P., Shen, S., Ng, W.K., and Tan, R.B., Formulation of Fe3O4/acrylate Co-polymer Nanocomposites as Potential drug Carriers, Drug Deliv., 2008, vol. 15, pp. 177–183.PubMedCrossRefGoogle Scholar
  29. Pisanic, T.R., Blackwell, J.D., Shubayev, V.I., Finones, R.R., Jin, S., Nanotoxicity of Iron Oxide Nanoparticle Internalization in Growing Neurons, Biomaterials, 2007, vol. 28, pp. 2572–2581.PubMedCrossRefGoogle Scholar
  30. Platonov, A.E., Statistical Analysis in Biology and Medicine: Challenges, Terminology, and Computer Methods, Moscow, Izd. Ros. Akad. Med. Nauk, 2000.Google Scholar
  31. Shinkai, M., Yanase, M., Honda, H., Wakabayashi, T., Yoshida, J., and Kobayashi, T., Intracellular Hyperthermia for Cancer Using Magnetite Cationic Liposomes: In Vitro Study, Jpn. J. Cancer Res., 1996, vol. 87, pp. 1179–1183.PubMedGoogle Scholar
  32. Sukach, A.N., Characteristics of Human Embryonic Neuronal Cells, Obtained by Non-enzymatic Method, Tsitologiia,, 2005, vol. 47, no. 3, pp. 207–213.PubMedGoogle Scholar
  33. Takahashi, K., Mitsui, M., Takeuchi, K., Uwabe, Y., Kobayashi, K., Sawasaki, Y., and Matsuoka, T., Preservation of the Characteristics of the Cultured Human Type 2 Alveolar Epithelial Cells, Lung, 2004, vol. 182, pp. 213–228.PubMedCrossRefGoogle Scholar
  34. Takezawa, T., Mori, Y., Yonaha, T., and Yoshizato, K., Characterization of Morphology and Cellular Metabolism during Spheroid Formation, Exp. Cell Res., 1993, vol. 208, pp. 430–441.PubMedCrossRefGoogle Scholar
  35. Trehin, R., Figueiredo, J.L., Pittet, M., Weissleder, R., Josephson, L., and Mahmood, U., Fluorescent Nanoparticle Uptake for Brain Tumor Visualization, Neoplasia, 2006, vol. 8, pp. 302–311.PubMedCrossRefGoogle Scholar
  36. Weissleder, R., Bogdanov, A., Neuwelt, E.A., and Papisov, M., Long Circulating iron Oxides for MR Imaging, Adv. Drug. Del. Rev., 1995, vol. 16, pp. 321–234.CrossRefGoogle Scholar
  37. Yoshida, J. and Kobayashi, T., Intracellular Hyperthermia for Cancer using Magnetite Cationic Liposomes, J. Magn. Magn. Mater., 1999, vol. 194, pp. 176–184.CrossRefGoogle Scholar
  38. Zhang, Y. and Zhang, J., Surface Modification of Monodisperse Magnetite Nanoparticles for Improved Intracellular Uptake to Breast Cancer Cells, J. Colloid Interface Sci., 2005, vol. 283, pp. 352–357.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2011

Authors and Affiliations

  • A. N. Sukach
    • 1
    • 2
  • A. S. Lebedinskii
    • 1
  • V. I. Grishchenko
    • 1
  • T. D. Lyashenko
    • 2
  1. 1.Institute for Problems of Cryobiology and CryomedicineNational Academy of Sciences of UkraineKharkovUkraine
  2. 2.Skovoroda National Pedagogical UniversityKharkovUkraine

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