Study on Fe3O4 Magnetic Nanoparticles ‎Size Effect on Temperature Distribution ‎of Tumor in Hyperthermia: A Finite ‎Element Method ‎

Document Type : Research Paper


1 Radiation Applications Research School, Nuclear Science and Technology Research ‎Institute, PO Box 31485-498, Karaj, Iran. ‎

2 Secondary Standard Dosimetry Laboratory (SSDL), Pars Isotope, Karaj, Iran. ‎


   In recent years, Hyperthermia has been used as an emerging technique for cancer treatment, especially for localized tumors. One of the promising cancer treatment approaches is magnetic nanoparticle (MNPs) Hyperthermia. In this theoretical work, the temperature distribution of a common tumor over the different sizes of Fe3O4 magnetic nanoparticles, namely 25, 50, 100, and 200 nm, was studied via the finite element method. A two-dimensional method was used to simulate the tumor tissue, in which nanoparticles were incorporated and dispersed into the tumor uniformly. The bio heat transfer equation (BHTE) was applied to calculate the thermal processes in the human body. Results elucidated that decreasing magnetic nanoparticle size caused more temperature rise in the tumor cell during the Hyperthermia treatment, which led to better performance of the treatment. Finally, simulation results showed that the Fe3O4 magnetic nanoparticles with the sizes of 50-100 nm were applicable for Hyperthermia therapy with the optimum cellular uptake.


  1. Nacev, A. N., (2013). “Magnetic drug targeting developing the basics”, Department of Bioengineering, University of Maryland.
  2. Wust, P., Hildebrandt, B.,  Sreenivasa, G., Rau, B., Gellermann, J., Riess, H., Felix, R., Schlag, P. (2002). “Hyperthermia in combined treatment of cancer”, The lancet oncology, 3: 487-497.
  3. Van der Zee, J., (2002). “Heating the patient: a promising approach?”, Ann. Oncol., 13: 1173-1184.
  4. Vasilakaki, M., Binns, C., Trohidou, K. N., (2002). “Susceptibility losses in heating of magnetic core/shell nanoparticles for hyperthermia: a Monte Carlo study of shape and size effects”, Nanoscale, 7: 7753-7762.
  5. Holligan, D., Gillies, G., Dailey, J., (2003). “Magnetic guidance of ferrofluidic nanoparticles in an in vitro model of intraocular retinal repair”, Nanot, 14: 661.
  6. Ganguly, R., Gaind, A. P., Sen, S., Puri, I. K., (2005). “Analyzing ferrofluid transport for magnetic drug targeting”, J. Magn. Magn. Mater., 289: 331-334.
  7. Jurgons, R., Seliger, C., Hilpert, A., Trahms, L., Odenbach, S., Alexiou, C.,  (2005). “Drug loaded magnetic nanoparticles for cancer therapy”, J. Phys.: Condens. Matter, 18: S2893.
  8. Kallumadil, M., Tada, M., Nakagawa, T., Abe, M., Southern, P., Pankhurst, Q. A., (2009). “Corrigendum to Suitability of commercial colloids for magnetic hyperthermia”[J. Magn. Magn. Mater. 321: 1509-1513], J. Magn. Magn. Mater., 321: 3650-3651.
  9. Laurent, S., Dutz, S., Häfeli, U. O., Mahmoudi, M., (2011). “Magnetic fluid hyperthermia: focus on superparamagnetic iron oxide nanoparticles”, Adv. Colloid Interface Sci., 166: 8-23.
  10. Fortin, J. P., Wilhelm, C., Servais, J., Ménager, C., Bacri, J. C., Gazeau, F., (2007). “Size-sorted anionic iron oxide nanomagnets as colloidal mediators for magnetic hyperthermia”, J. Am. Chem. Soc, 129: 2628-2635.
  11. Chen, R., Christiansen, M. G., Anikeeva, P., (2013). “Maximizing hysteretic losses in magnetic ferrite nanoparticles via model-driven synthesis and materials optimization”, ACS nano, 7: 8990-9000.
  12. Basti, H., Hanini, A., Levy, M., Tahar, L. B., Herbst, F., Smiri, L. S., Kacem, K., Gavard, J., Wilhelm, C., Gazeau, F., Chau, F., Ammar, S., (2014). “Size tuned polyol-made Zn 0.9 M 0.1 Fe 2 O 4 (M = Mn, Co, Ni) ferrite nanoparticles as potential heating agents for magnetic hyperthermia: from synthesis control to toxicity survey”, Materials Research Express, 1: 045047.
  13. Hatamzadeh, M., Johari-Ahar, M., Jaymand, M., (2012). “In situ chemical oxidative graft polymerization of aniline from Fe3O4 nanoparticles”, International Journal of Nanoscience and Nanotechnology, 8: 51-60.
  14. Khan, S., Pathak, B., Fulekar, M., (2017). “Spherical Surfaced Magnetic (Fe3O4) Nanoparticles as Nano Adsorbent Material for Treatment of Industrial Dye Effluents”, International Journal of Nanoscience Nanotechnology, 13: 169-175.
  15. Banisharif, A.,  Hakim Elahi, S.  Anaraki Firooz, A., Khodadadi, A. A, Mortazavi, Y., (2013). “TiO2/Fe3O4 nanocomposite photocatalysts for enhanced photo-decolorization of congo red dye”, International Journal of Nanoscience and Nanotechnology, 9: 193-202.
  16. Pankhurst, Q. A., Connolly, J., Jones, S. K., Dobson, J., (2003). “Applications of magnetic nanoparticles in biomedicine”, J. Phys. D: Appl. Phys., 36: R167.
  17. Pankhurst, Q. A., Thanh, N. T. K, Jones, S. K., Dobson, J., (2009). “Progress in applications of magnetic nanoparticles in biomedicine”, J. Phys. D: Appl. Phys., 42: 224001.
  18. Mahmoudi, M., Serpooshan, V., Laurent, S. (2011). “Engineered nanoparticles for biomolecular imaging”, Nanoscale, 3: 3007-3026.
  19. Krukemeyer, M. G., Krenn, V., Jakobs, M., Wagner, W., (2012). “Mitoxantrone-iron oxide biodistribution in blood, tumor, spleen, and liver—magnetic nanoparticles in cancer treatment”, J. Surg. Res., 175: 35-43.
  20. Zhu, L., Zhou, Z., Mao, H., Yang, L.,  (2017). “Magnetic nanoparticles for precision oncology: theranostic magnetic iron oxide nanoparticles for image-guided and targeted cancer therapy”, Nanomedicine, 12: 73-87.
  21. Gutierrez-Guzman, D., Lizardi, L., Otálora, J., Landeros, P., (2017). “Hyperthermia in low aspect-ratio magnetic nanotubes for biomedical applications”, Appl. Phys. Lett., 110: 133702.
  22. LeBrun, A., Joglekar, T., Bieberich, C., Ma, R., Zhu, L., (2017). “Treatment Efficacy for Validating MicroCT-Based Theoretical Simulation Approach in Magnetic Nanoparticle Hyperthermia for Cancer Treatment”, J. Heat Transfer, 139: 051101.
  23. Fang, C. H., Tsai, P. I., Huang, S. W., Sun, J. S., Chang, J. Z. C., Shen, H. H., Chen, S. Y., Lin, F. H., Hsu, L. T., Chen, Y. C., (2017). “Magnetic hyperthermia enhance the treatment efficacy of peri-implant osteomyelitis”, BMC Infect. Dis., 17: 516.
  24. Shabestari Khiabani, S., M. Farshbaf, A. Akbarzadeh, S. Davaran, (2017). “Magnetic nanoparticles: preparation methods, applications in cancer diagnosis and cancer therapy”, Artificial cells, nanomedicine, and biotechnology, 45:6-17.
  25. Hoopes, P. J., Moodie, K. L., Petryk, A. A., Petryk, J. D., Sechrist, S., Gladstone, D. J., Steinmetz, N. F., Veliz, F. A., Bursey, A. A.,  Wagner, R. J., (2017). “Hypo-fractionated radiation, magnetic nanoparticle hyperthermia and a viral immunotherapy treatment of spontaneous canine cancer”,  Energy-based Treatment of Tissue and Assessment IX, International Society for Optics and Photonics, 1006605.
  26. Dutz, S., Hergt, R., (2014). “Magnetic particle hyperthermia—a promising tumour therapy?”, Nanot, 25: 452001.
  27. Yi, G. q., Gu, B., Chen, L. k., (2014). “The safety and efficacy of magnetic nano-iron hyperthermia therapy on rat brain glioma”, Tumour Biol., 35: 2445-2449.
  28. Asín, L.,  Ibarra, M., Tres, A., Goya, G., (2012). “Controlled cell death by magnetic hyperthermia: effects of exposure time, field amplitude, and nanoparticle concentration”, Pharm. Res., 29: 1319-1327.
  29. Balivada, S., Rachakatla, R. S., Wang, H., Samarakoon, T. N., Dani, R. K., Pyle, M., Kroh, F. O., Walker, B., Leaym, X., Koper, O. B., (2010). “A/C magnetic hyperthermia of melanoma mediated by iron (0)/iron oxide core/shell magnetic nanoparticles: a mouse study”, BMC Cancer, 10:119.
  30. Hergt, R., Dutz, S., Müller, R., Zeisberger, M., (2006). “Magnetic particle hyperthermia: nanoparticle magnetism and materials development for cancer therapy, J. Phys.: Condens. Matter, 18: S2919.
  31. Harabech, M., Leliaert, J., Coene, A., Crevecoeur, Van Roost, G. D., Dupré, L.,  (2017). “The effect of the magnetic nanoparticle’s size dependence of the relaxation time constant on the specific loss power of magnetic nanoparticle hyperthermia”, J. Magn. Magn. Mater., 426: 206-210.
  32. Figuerola, A., Corato, R.I., Manna, L., Pellegrino, T., (2010). “From Iron Oxide Nanoparticles towards Advanced Iron-Based Inorganic Materials Designed for Biomedical Applications”, Pharmacol. Res., 62: 126-143.
  33. Veiseh, O., Gunn, J., Zhang, M., (2010). “Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging”, Adv. Drug Deliv. Rev., 62: 284–304.
  34. Sun, C., Lee, J., Zhang, M., (2008). “Magnetic nanoparticles in MR imaging and drug delivery”, Adv. Drug Deliv. Rev. , 60: 1252–1265.
  35. Thapa, D., Palkar, V., Kurup, M., Malik, S., (2004). “Properties of magnetite nanoparticles synthesized through a novel chemical route”, Mater. Lett., 58: 2692-2694.
  36. Hilger, I., Hiergeist, R., Hergt, R., Winnefeld, K., Schubert, H., Kaiser, W. A., (2002). “Thermal ablation of tumors using magnetic nanoparticles: an in vivo feasibility study”, Invest. Radiol., 37: 580-586.
  37. Giustini, A. J., Petryk, A. A., Cassim, S. M., Tate, J. A., Baker, I., Hoopes, P. J., (2010). “Magnetic nanoparticle hyperthermia in cancer treatment”, Nano Life, 1: 17-32.
  38. Pennes, H. H., (1948). “Analysis of tissue and arterial blood temperatures in the resting human forearm”, J. Appl. Physiol., 1: 93-122.
  39. Ambrosio, V. D., Dughiero, F., (2007). “Numerical model for RF capacitive regional deep hyperthermia in pelvic tumors”, Med Bio Eng Comput, 45: 459-466.
  40. Tompkins, D., Vanderby, R., Klein, S., Beckman, W., Steeves, R., Frye, D., Paliwal, B., (1994). “Temperature-dependent versus constant-rate blood perfusion modelling in ferromagnetic thermoseed hyperthermia: results with a model of the human prostate”, International journal of hyperthermia: the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, 10: 517-536.
  41. Skomski, R., Balamurugan, B., Manchanda, P., Chipara, M., Sellmyer, D.J., (2017). “Size Dependence of Nanoparticle Magnetization”, IEEE Trans. Magn., 53.
  42. Alexiou, C., Diehl, D., Henninger, P., Iro, H., Rockelein, R., Schmidt, W., Weber, H., (2006). “A high field gradient magnet for magnetic drug targeting”, ITAS, 16:1527-1530.
  43. Fannin, P., (1991). “Measurement of the Neel relaxation of magnetic particles in the frequency range 1 kHz to 160 MHz”, J. Phys. D: Appl. Phys., 24: 76.
  44. Atkinson, W. J., Brezovich, I. A., Chakraborty, D.P., (1984). “Usable frequencies in hyperthermia with thermal seeds”, IEEE Trans. Biomed. Eng., 70-75.
  45. Callister, W. D., (2001). “Fundamentals of Materials Science and Engineering”, fifth ed., John Wiley & Sons, Inc., The University of Utah.
  46. Reddy, J., (2005). “An introduction to the finite element method”, 3rd ed., MC Graw-Hill Series in Mechanical Engineering.
  47. Malekie, S.,  Ziaie, F., (2017). “A two-dimensional simulation to predict the electrical behavior of carbon nanotube/polymer composites”, J. Polym. Eng., 37: 205-210.
  48. Wang, Z. L., Gao, R. P., Pan, Z. W., Dai, Z. R., (2001). “Nano-scale mechanics of nanotubes, nanowires, and nanobelts”, Adv. Eng. Mater., 3: 657.
  49. Guo, X., Wu, Z., Li, W., Wang, Z., Li, Q., Kong, F., Zhang, H., Zhu, X., Du, Y.P., Jin, Y., (2016). “Appropriate size of magnetic nanoparticles for various bioapplications in cancer diagnostics and therapy”, ACS Applied Materials & Interfaces, 8: 3092-3106.
  50. Ovejero, J. G., Cabrera, D., Carrey, J., Valdivielso, T., Salas, G., Teran, F. J., (2016). “Effects of inter-and intra-aggregate magnetic dipolar interactions on the magnetic heating efficiency of iron oxide nanoparticles”, PCCP, 18: 10954-10963.
  51. Rajabi, A., Malekie, S., (2017). “Simulation of magnetic nanoparticle hyperthermia for curing the tumors using finite element method”,  Secon Nanomedicine and Nanosafety Conference (NMNS 2017), Tehran University of Medical Sciences.
  52. Valente, A., Loureiro, F., Di Bartolo, L., Mansur, W. J., (2018). “Computer simulation of hyperthermia with nanoparticles using an OcTree finite volume technique”, International Communications in Heat Mass Transfer, 91: 248-255.
  53. Taloub, S., Hobar, F., Astefanoaei, I., Dumitru, I., Caltun, O. F., (2016). “FEM Investigation of coated magnetic nanoparticles for hyperthermia”, Nanoscience and Nanotechnology, 6: 55-61.
  54. Dahwi, A. A., (2017). “Finite Element Simulation, Characterization and Transportation of Magnetic Nanoparticles under the Impact of Magnetic Field in Blood Vessels”, Global Journal of Pure Applied Mathematics, 13: 7771-7784.