Magnetic hyperthermia therapy enhances the chemoradiosensitivity of glioblastoma
Abstract Glioblastoma (GBM) is the most common primary brain cancer and is resistant to standard-of-care chemoradiation therapy (CRT). Magnetic hyperthermia therapy (MHT) exposes magnetic iron oxide nanoparticles (MIONPs) to an alternating magnetic field (AMF) to generate local hyperthermia. This st...
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Nature Portfolio
2025-03-01
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| Online Access: | https://doi.org/10.1038/s41598-025-95544-3 |
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| author | Daniel Rivera Alexandros Bouras Milena Mattioli Maria Anastasiadou Anna Chiara Pacentra Olivia Pelcher Corrine Koziel Alexander J. Schupper Tori Chanenchuk Hayden Carlton Robert Ivkov Constantinos G. Hadjipanayis |
| author_facet | Daniel Rivera Alexandros Bouras Milena Mattioli Maria Anastasiadou Anna Chiara Pacentra Olivia Pelcher Corrine Koziel Alexander J. Schupper Tori Chanenchuk Hayden Carlton Robert Ivkov Constantinos G. Hadjipanayis |
| author_sort | Daniel Rivera |
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| description | Abstract Glioblastoma (GBM) is the most common primary brain cancer and is resistant to standard-of-care chemoradiation therapy (CRT). Magnetic hyperthermia therapy (MHT) exposes magnetic iron oxide nanoparticles (MIONPs) to an alternating magnetic field (AMF) to generate local hyperthermia. This study evaluated MHT-mediated enhancement of CRT in preclinical GBM models. Cell viability and apoptosis were assessed in GBM cell lines after water bath heating with radiation and/or temozolomide. Heating efficiency of MIONPs after intracranial delivery was measured in healthy mice. MHT with CRT was performed in syngeneic and patient-derived xenograft (PDX) GBM tumors. Tissue sections were analyzed for γ-H2AX, HSP90, CD4 + T cells, and microglial cells. Tumor burden and survival were assessed. Hyperthermia with radiation and temozolomide significantly reduced cell viability and increased apoptosis. Hyperthermia predominantly exhibited additive to synergistic interactions with both treatment modalities and reduced doses needed for tumor cell growth inhibition. In vivo, MHT with CRT decreased tumor burden and increased survival in PDX and syngeneic models. Immunohistochemistry showed increased γ-H2AX, HSP90, microglial activation, and CD4 + T cells after MHT in combination with CRT. Overall, adjuvant hyperthermia enhances CRT efficacy in GBM cells, with MHT improving survival outcomes in rodents. Sufficient intracranial heating and MIONP retention for repeated treatments was achieved, supporting further clinical translation. |
| format | Article |
| id | doaj-art-2b4f34a4e53a48d9a1a7c6178e3370e2 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-2b4f34a4e53a48d9a1a7c6178e3370e22025-08-20T02:49:30ZengNature PortfolioScientific Reports2045-23222025-03-0115111510.1038/s41598-025-95544-3Magnetic hyperthermia therapy enhances the chemoradiosensitivity of glioblastomaDaniel Rivera0Alexandros Bouras1Milena Mattioli2Maria Anastasiadou3Anna Chiara Pacentra4Olivia Pelcher5Corrine Koziel6Alexander J. Schupper7Tori Chanenchuk8Hayden Carlton9Robert Ivkov10Constantinos G. Hadjipanayis11Brain Tumor Nanotechnology Laboratory, UPMC Hillman Cancer CenterBrain Tumor Nanotechnology Laboratory, UPMC Hillman Cancer CenterBrain Tumor Nanotechnology Laboratory, UPMC Hillman Cancer CenterDepartment of Neurological Surgery, Icahn School of Medicine at Mount SinaiBrain Tumor Nanotechnology Laboratory, UPMC Hillman Cancer CenterBrain Tumor Nanotechnology Laboratory, UPMC Hillman Cancer CenterBrain Tumor Nanotechnology Laboratory, UPMC Hillman Cancer CenterDepartment of Neurological Surgery, Icahn School of Medicine at Mount SinaiDepartment of Neurological Surgery, Icahn School of Medicine at Mount SinaiDepartment of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of MedicineDepartment of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of MedicineBrain Tumor Nanotechnology Laboratory, UPMC Hillman Cancer CenterAbstract Glioblastoma (GBM) is the most common primary brain cancer and is resistant to standard-of-care chemoradiation therapy (CRT). Magnetic hyperthermia therapy (MHT) exposes magnetic iron oxide nanoparticles (MIONPs) to an alternating magnetic field (AMF) to generate local hyperthermia. This study evaluated MHT-mediated enhancement of CRT in preclinical GBM models. Cell viability and apoptosis were assessed in GBM cell lines after water bath heating with radiation and/or temozolomide. Heating efficiency of MIONPs after intracranial delivery was measured in healthy mice. MHT with CRT was performed in syngeneic and patient-derived xenograft (PDX) GBM tumors. Tissue sections were analyzed for γ-H2AX, HSP90, CD4 + T cells, and microglial cells. Tumor burden and survival were assessed. Hyperthermia with radiation and temozolomide significantly reduced cell viability and increased apoptosis. Hyperthermia predominantly exhibited additive to synergistic interactions with both treatment modalities and reduced doses needed for tumor cell growth inhibition. In vivo, MHT with CRT decreased tumor burden and increased survival in PDX and syngeneic models. Immunohistochemistry showed increased γ-H2AX, HSP90, microglial activation, and CD4 + T cells after MHT in combination with CRT. Overall, adjuvant hyperthermia enhances CRT efficacy in GBM cells, with MHT improving survival outcomes in rodents. Sufficient intracranial heating and MIONP retention for repeated treatments was achieved, supporting further clinical translation.https://doi.org/10.1038/s41598-025-95544-3GlioblastomaMagnetic hyperthermia therapyMagnetic iron-oxide nanoparticlesRadiation therapyTemozolomideChemoradiation |
| spellingShingle | Daniel Rivera Alexandros Bouras Milena Mattioli Maria Anastasiadou Anna Chiara Pacentra Olivia Pelcher Corrine Koziel Alexander J. Schupper Tori Chanenchuk Hayden Carlton Robert Ivkov Constantinos G. Hadjipanayis Magnetic hyperthermia therapy enhances the chemoradiosensitivity of glioblastoma Scientific Reports Glioblastoma Magnetic hyperthermia therapy Magnetic iron-oxide nanoparticles Radiation therapy Temozolomide Chemoradiation |
| title | Magnetic hyperthermia therapy enhances the chemoradiosensitivity of glioblastoma |
| title_full | Magnetic hyperthermia therapy enhances the chemoradiosensitivity of glioblastoma |
| title_fullStr | Magnetic hyperthermia therapy enhances the chemoradiosensitivity of glioblastoma |
| title_full_unstemmed | Magnetic hyperthermia therapy enhances the chemoradiosensitivity of glioblastoma |
| title_short | Magnetic hyperthermia therapy enhances the chemoradiosensitivity of glioblastoma |
| title_sort | magnetic hyperthermia therapy enhances the chemoradiosensitivity of glioblastoma |
| topic | Glioblastoma Magnetic hyperthermia therapy Magnetic iron-oxide nanoparticles Radiation therapy Temozolomide Chemoradiation |
| url | https://doi.org/10.1038/s41598-025-95544-3 |
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