The effect of thermotherapy using magnetic nanoparticles on rat malignant glioma
- 1.4k Downloads
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.
Keywordsglioma magnetic nanoparticles rat thermotherapy
Unable to display preview. Download preview PDF.
- 1.Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, Radiotherapy plus concomitant and adjuvant temozolomide for glioblastomaN Engl J Med 352: 987–996, 2005CrossRefPubMedGoogle Scholar
- 3.Jordan A, Wust P, Fahling H, John W, Hinz A, Felix R, Inductive heating of ferrimagnetic particles and magnetic fluids: physical evaluation of their potential for hyperthermia Int J Hyperther9: 51–68, 1993Google Scholar
- 4.Jordan A, Wust P, Scholz R, Tesche B, Fahling H, Mitrovics T, Vogl T, Cervos-Navarro J, Felix R, Cellular uptake of magnetic fluid particles and their effects on human adenocarcinoma cells exposed to AC magnetic fields in vitroInt J Hyperther12: 705–722, 1996Google Scholar
- 5.Jordan A, Scholz R, Wust P, Fahling H, Krause J, Wlodarczyk W, Sander B, Vogl T, Felix R, Effects of magnetic fluid hyperthermia (MFH) on C3H mammary carcinoma in vivoInt J Hyperther13: 587–605, 1997Google Scholar
- 8.Johannsen M, Thiesen B, Gneveckow U, Taymoorian K, Waldöfner N, Scholz R, Deger S, Jung K, Loening S, Jordan A: Thermotherapy using magnetic nanoparticles combined with external radiation in an orthotopic Dunning rat model of prostate cancer. Prostate Epub, 20th August 2005Google Scholar
- 14.Johannsen M, Gneveckow U, Eckelt L, Feussner A, Waldoefner N, Scholz R, Deger S, Wust P, Loening S, Jordan A: Clinical hyperthermia of prostate cancer using magnetic nanoparticles: presentation of a new interstitial technique. Int J Hyperther 21: 637–647, 2005Google Scholar