Summary
Thermotherapy using magnetic nanoparticles is a new technique for interstitial hyperthermia and thermoablation based on magnetic field-induced excitation of biocompatible superparamagnetic nanoparticles. To evaluate the potential of this technique for minimally invasive treatment, we carried out a systematic analysis of its effects on experimental glioblastoma multiforme in a rat tumor model.
Tumors were induced by implantation of RG-2-cells into the brains of 120 male Fisher rats. Animals were randomly allocated to 10 groups of 12 rats each, including controls. Animals received two thermotherapy treatments following a single intratumoral injection of two different magnetic fluids (dextran- or aminosilane-coated iron-oxide nanoparticles). Treatment was carried out on days four and six after tumor induction using an alternating magnetic field applicator system operating at a frequency of 100 kHz and variable field strength of 0–18 kA/m. The effectiveness of treatment was determined by the survival time of the animals and histopathological examinations of the brain and the tumor.
Thermotherapy with aminosilane-coated nanoparticles led up to 4.5-fold prolongation of survival over controls, while the dextran-coated particles did not indicate any advantage. Intratumoral deposition of the aminosilane-coated particles was found to be stable, allowing for serial thermotherapy treatments without repeated injection. Histological and immunohistochemical examinations after treatment revealed large necrotic areas close to particle deposits, a decreased proliferation rate and a reactive astrogliosis adjacent to the tumor.
Thus, localized interstitial thermotherapy with magnetic nanoparticles has an antitumoral effect on malignant brain tumors. This method is suitable for clinical use and may be a novel strategy for treating malignant glioma, which cannot be treated successfully today. The optimal treatment schedules and potential combinations with other therapies need to be defined in further studies.
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Acknowledgements
This work was supported by the EFRE Project “NanoMed”, Nanotechnology in Medicine, No. 2000-22006 2ue/2 and the Federal Ministry of Education and Research, Germany (BMB+F), Mehrschalige Nano-Carrier (MNC) für die zellspezifische Thermochemotherapie von Krebs” No. 0312009.
We gratefully thank Dr. James M. Gallo, Department of Pharmacology, Fox Chase Cancer Center, Philadelphia, PA, USA, for providing the RG-2 cell-line, Willi Schmidt for help with the statistical analysis and Erik Grieger for his expert technical assistance.
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Jordan, A., Scholz, R., Maier-Hauff , K. et al. The effect of thermotherapy using magnetic nanoparticles on rat malignant glioma. J Neurooncol 78, 7–14 (2006). https://doi.org/10.1007/s11060-005-9059-z
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DOI: https://doi.org/10.1007/s11060-005-9059-z