# Translational Application of Magnetic Hyperthermia Therapy with Adjuvant Therapies for Glioblastoma

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $56,103

## Abstract

Project Summary/Abstract
Glioblastoma (GBM) remains a fatal brain cancer for which there is no cure. Maximal safe tumor resection
combined with adjuvant therapies such as fractionated external beam radiation therapy (RT) and temozolomide
(TMZ) chemotherapy, known as chemoradiation (CRT), has provided the greatest benefit to GBM patients.
However, local recurrence occurs in most patients due to invasive therapy-resistant infiltrating cancer cells at
the tumor margin. Magnetic hyperthermia therapy (MHT) is a powerful nanotechnology-based treatment that
may enhance the effects of CRT. MHT consists of local heat generation in the tumor region through direct
delivery of magnetic iron-oxide nanoparticles (MIONPs) that are activated by exposure to an external alternating
magnetic field (AMF) that is safe to normal cells. The AMF interacts with the magnetic dipoles of the MIONPs to
generate local heat and hyperthermia. Human clinical trials have demonstrated overall survival benefits of MHT
with fractionated RT in recurrent GBM resulting in European approval. Current MHT strategies, however,
require high concentrations of nontargeted MIONPs (>100 mg/ml; 50-100mg Fe/g of tumor) delivered by
injection with leakback and without image-guided control of energy deposition. As a result, normal tissue
injury limits MHT effectiveness and treatment of the infiltrative tumor margins is poorly defined, which
compromises MHT efficacy. Our proposal is designed to address these challenges, optimize the translational
potential for enhanced MHT of GBM in combination with CRT, and study some of the mechanisms by which
MHT invokes tumor cell death, blood-brain and blood-tumor barrier permeability, and immune cell recruitment
when administered alone and in combination with CRT in vitro and in a mouse model. We have recently
completed a pilot study in spontaneous canine gliomas demonstrating feasibility and safety of image-guided
MIONP delivery alone. We hypothesize that MHT will enhance CRT of GBM. We propose to evaluate the
enhancement of CRT by MHT in mouse GBM models with an innovative MIONP formulation. We have
Preliminary Data that demonstrate intracranial hyperthermia with a 3-fold increase in TMZ concentration within
GBM tumors, leading to a robust antitumor effect with increased survival after MHT + CRT in a therapy-resistant
rodent glioma model.

## Key facts

- **NIH application ID:** 10599714
- **Project number:** 3R01CA247290-03S1
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Constantinos George Hadjipanayis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $56,103
- **Award type:** 3
- **Project period:** 2019-12-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10599714

## Citation

> US National Institutes of Health, RePORTER application 10599714, Translational Application of Magnetic Hyperthermia Therapy with Adjuvant Therapies for Glioblastoma (3R01CA247290-03S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10599714. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*