Introduction: Local hyperthermia generated by magnetic nanoparticles (MNPs) has recently been described in patients for the thermotherapy of recurrent glioblastoma (GBM) after intratumoral implantation in high concentration. Here we describe the use of novel magnetic iron-oxide nanoparticles (IONPs) embedded on a synthetic clay matrix (laponite) for thermotherapy of experimental GBM that acheive high temperatures at low concentrations with safe applied magnetic fields (AMF).
Methods: A comparison of temperature elevation was made with standard IONPs (6 mg/ml; mean diameter of 15 nm) and laponite-embedded IONPs (3 mg/ml; mean diameter of 13 nm) after application of an AMF (288 kHz) for 10 min. Therapy-resistant human GBM cells (U87wtEGFR and U87?EGFRvIII) that overexpress the wild-type (wt) EGFR or the deletion mutant EGFRvIII, were treated with laponite-embedded IONPs (3 mg/ml) or control (medium). After 24 h of incubation with the laponite-embedded IONPs, GBM cells were treated with an AMF (288 kHz) for 10 min. Cell survival and proliferation were assessed. Toxicity studies were performed with human GBM cells (U87?EGFRvIII) and human foreskin fibroblasts (HFF) after treatment with laponite-embedded IONPs (12, 24, and 48 h) or control (medium) and no application of AMF.
Results: A greater than thirteen-fold elevation in temperature was achieved after application of an AMF with laponite-embedded IONPs (68 °C) in comparison to standard IONPs (5 °C) double in concentration. A large drop in GBM cell survival and proliferation was found in all therapy-resistant cell lines after application of an AMF and thermotherapy. Minimal to no toxicity was found in GBM or HFF cells at 12, 24, and 48 h of treatment with laponite-embedded IONPs in comparison to control treatment of cells.
Conclusions: Laponite-embedded IONPs represent an ideal magnetic nanoparticle composite material for the thermotherapy of experimental GBM at low concentration when exposed to safe AMF.
Patient Care: This translational work provides feasibility studies for possible improvement of currently used magnetic nanoparticles for thermotherapy of GBM.
Learning Objectives: 1. Thermotherapy of GBM by magnetic nanoparticles
2. Hyperthermia comparison of laponite-embedded IONPs to standard IONPs
3. Toxicity of laponite-embedded IONPs with no applied magnetic fields.
4. Antitumor effect of hyperthermia generation of laponite-embedded IONPs with applied magnetic fields.