INTRODUCTION: Magnetic nanoparticles (NPs) represent a tool for use in magnetic resonance imaging (MRI)-guided thermoablation of tumors using an external high-frequency (HF) magnetic field. To avoid local overheating, perovskite NPs with a lower Curie temperature (T c) were proposed for use in thermotherapy. However, deposited power decreases when approaching the Curie temperature and consequently may not be sufficient for effective ablation. The goal of the study was to test this hypothesis. METHODS: Perovskite NPs (T c =66°C-74°C) were characterized and tested both in vitro and in vivo. In vitro, the cells suspended with NPs were exposed to a HF magnetic field together with control samples. In vivo, a NP suspension was injected into a induced tumor in rats. Distribution was checked by MRI and the rats were exposed to a HF field together with control animals. Apoptosis in the tissue was evaluated. RESULTS AND DISCUSSION: In vitro, the high concentration of suspended NPs caused an increase of the temperature in the cell sample, leading to cell death. In vivo, MRI confirmed distribution of the NPs in the tumor. The temperature in the tumor with injected NPs did not increase substantially in comparison with animals without particles during HF exposure. We proved that the deposited power from the NPs is too small and that thermoregulation of the animal is sufficient to conduct the heat away. Histology did not detect substantially higher apoptosis in NP-treated animals after ablation. CONCLUSION: Magnetic particles with low T c can be tracked in vivo by MRI and heated by a HF field. The particles are capable of inducing cell apoptosis in suspensions in vitro at high concentrations only. However, their effect in the case of extracellular deposition in vivo is questionable due to low deposited power and active thermoregulation of the tissue.

Department of Analytical Chemistry Institute of Chemical Technology

Department of Inorganic Technology Faculty of Chemical Technology University of Pardubice; SYNPO akciová společnost Pardubice

Department of Magnetics and Superconductors Institute of Physics Czech Academy of Sciences Prague

Department of Neuroscience Institute of Experimental Medicine

Diabetes Center Institute for Clinical and Experimental Medicine Prague Czech Republic

MR Unit Radiodiagnostic and Interventional Radiology Department Institute for Clinical and Experimental Medicine Prague

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Torres-Lugo M, Rinaldi C. Thermal potentiation of chemotherapy by magnetic nanoparticles. Nanomedicine. 2013;8(10):1689–1707. PubMed PMC

Cheng Y, Morshed RA, Auffinger B, Tobias AL, Lesniak MS. Multifunctional nanoparticles for brain tumor imaging and therapy. Adv Drug Deliv Rev. 2014;66:42–57. PubMed PMC

Palazzi M, Maluta S, Dall’Oglio S, Romano M. The role of hyperthermia in the battle against cancer. Tumori. 2010;96(6):902–910. PubMed

Verma J, Lal S, Van Noorden CJF. Nanoparticles for hyperthermic therapy: synthesis strategies and applications in glioblastoma. Int J Nanomedicine. 2014;9(1):2863–2877. PubMed PMC

Kossatz S, Ludwig R, Dahring H, et al. High therapeutic efficiency of magnetic hyperthermia in xenograft models achieved with moderate temperature dosages in the tumor area. Pharm Res. 2014;31(12):3274–3288. PubMed PMC

Hilger I, Hiergeist R, Hergt R, Winnefeld K, Schubert H, Kaiser WA. Thermal ablation of tumors using magnetic nanoparticles – an in vivo feasibility study. Invest Radiol. 2002;37(10):580–586. PubMed

Duguet E, Vasseur S, Mornet S, Devoisselle JM. Magnetic nanoparticles and their applications in medicine. Nanomedicine. 2006;1(2):157–168. PubMed

Rosensweig RE. Heating magnetic fluid with alternating magnetic field. J Magn Magn Mater. 2002;252(1–3):370–374.

Pankhurst QA, Connolly J, Jones SK, Dobson J. Applications of magnetic nanoparticles in biomedicine. J Phys D Appl Phys. 2003;36(13):R167–R181.

Pankhurst QA, Thanh NTK, Jones SK, Dobson J. Progress in applications of magnetic nanoparticles in biomedicine. J Phys D Appl Phys. 2009;42(22):224001.

Mornet S, Vasseur S, Grasset F, et al. Magnetic nanoparticle design for medical applications. Prog Solid State Chem. 2006;34(2–4):237–247.

Pollert E, Knizek K, Marysko M, Kaspar P, Vasseur S, Duguet E. New T-c-tuned magnetic nanoparticles for self-controlled hyperthermia. J Magn Magn Mater. 2007;316(2):122–125.

Pollert E, Kaman O, Veverka P, et al. Core-shell La1-xSrxMnO3 nanoparticles as colloidal mediators for magnetic fluid hyperthermia. Phil Trans R Soc A. 2010;368(1927):4389–4405. PubMed

Pollert E, Kaspar P, Zaveta K, Herynek V, Burian M, Jendelova P. Magnetic nanoparticles for therapy and diagnostics. IEEE Trans Magn. 2013;49(1):7–10.

Kaman O, Veverka P, Jirak Z, et al. The magnetic and hyperthermia studies of bare and silica-coated La0.75Sr0.25MnO3 nanoparticles. J Nano-part Res. 2011;13(3):1237–1252.

Veverka M, Zaveta K, Kaman O, et al. Magnetic heating by silica-coated Co-Zn ferrite particles. J Phys D Appl Phys. 2014;47(6):65503–65513.

Jendelova P, Herynek V, DeCroos J, et al. Imaging the fate of implanted bone marrow stromal cells labeled with superparamagnetic nanoparticles. Magn Reson Med. 2003;50(4):767–776. PubMed

Fabryova E, Jirak D, Girman P, et al. Effect of mesenchymal stem cells on the vascularization of the artificial site for islet transplantation in rats. Transplant Proc. 2014;46(6):1963–1966. PubMed

Zvatora P, Veverka M, Veverka P, et al. Influence of surface and finite size effects on the structural and magnetic properties of nanocrystalline lanthanum strontium perovskite manganites. J Solid State Chem. 2013;204:373–379.

Babic M, Horak D, Trchova M, et al. Poly(L-lysine)-modified iron oxide nanoparticles for stem cell labeling. Bioconjugate Chem. 2008;19(3):740–750. PubMed

Horak D, Babic M, Jendelova P, et al. D-Mannose-modified iron oxide nanoparticles for stem cell labeling. Bioconjugate Chem. 2007;18(3):635–644. PubMed

Saito H, Mitobe K, Ito A, et al. Self-regulating hyperthermia induced using thermosensitive ferromagnetic material with a low Curie temperature. Cancer Sci. 2008;99(4):805–809. PubMed PMC

Kuznetsov AA, Leontiev VG, Brukvin VA, et al. Local radiofrequency-induced hyperthermia using CuNi nanoparticles with therapeutically suitable Curie temperature. J Magn Magn Mater. 2007;311(1):197–203.