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Theranostics, 2025, 15 (7) | https://doi.org/10.7150/thno.103503
7-nm Mn0.5 Zn0.5Fe2O4 superparamagnetic iron oxide nanoparticle (SPION): a high-performance theranostic for MRI and hyperthermia applications
Joo Young Lee1*, Yi Rang Na2,3,4*, Chul Min Na1, Pyung Won Im1, Hyung Woo Park1, Min Kyu Kim1, Yona Kim1, Ji Hyeon You1, Dong Su Kang2,3, Hyo Eun Moon1, Hye Ran Park5, Min Gyu Kim6, Pilhan Kim7,8, Sung Hye Park9, Hye Won Youn10, Young Don Son11, Yasushi Takemura12, Chang Won Song13, Daishun Ling14#, Yuanzhe Piao15#, Sun Ha Paek1,16#
1Department of Neurosurgery, Cancer Research Institute, Seoul National University College of Medicine. Seoul 03080, Republic of Korea.
2Translational Immunology Lab, Department of Transdisciplinary Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea.
3Immunology Core Facility, Department of Translational Research Center, Biomedical Research Institute, Seoul National University Hospital, Republic of Korea.
4Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
5Department of Neurosurgery, Soonchunhyang University Seoul Hospital, Seoul 04401, Republic of Korea.
6Pohang Accelerator Laboratory (PAL) Pohang 37673, Republic of Korea.
7Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
8Korea Institute for Health Science and Technology (KIHST), Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
9Department of Pathology, Neuroscience Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
10Department of Nuclear Medicine, Seoul National University Hospital, Republic of Korea. Laboratory of Molecular Imaging and Therapy, Cancer Research Institute, Seoul National University College of Medicine, Republic of Korea.
11Department of Biomedical Engineering, Gachon University, Seongnam, Republic of Korea
12Department of Electrical and Computer Engineering, Yokohama National University Yokohama 240-8501, Japan.
13Department of Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
14Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, School of Biomedical Engineering, National Center for Translational Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, 200240, Shanghai, China; World Laureates Association (WLA) Laboratories, 201203, Shanghai, China.
15Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Seoul National University, Seoul 08826, Republic of Korea. Advanced Institutes of Convergence Technology, Suwon-si, Gyeonggi-do, Republic of Korea.
16Hypoxia/Ischemia Disease Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea. Advanced Institute of Convergence Technology, Seoul National University, Suwon16229, Republic of Korea.
*Equally contributing first authors.
#Equally contributing co-corresponding authors.
Corresponding authors: Diashun Ling Ph. D., Yuanzhe Piao Ph. D., Sun Ha Paek MD, Ph. D. (Main corresponding author)
1Department of Neurosurgery, Cancer Research Institute, Seoul National University College of Medicine. Seoul 03080, Republic of Korea.
2Translational Immunology Lab, Department of Transdisciplinary Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea.
3Immunology Core Facility, Department of Translational Research Center, Biomedical Research Institute, Seoul National University Hospital, Republic of Korea.
4Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
5Department of Neurosurgery, Soonchunhyang University Seoul Hospital, Seoul 04401, Republic of Korea.
6Pohang Accelerator Laboratory (PAL) Pohang 37673, Republic of Korea.
7Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
8Korea Institute for Health Science and Technology (KIHST), Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
9Department of Pathology, Neuroscience Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
10Department of Nuclear Medicine, Seoul National University Hospital, Republic of Korea. Laboratory of Molecular Imaging and Therapy, Cancer Research Institute, Seoul National University College of Medicine, Republic of Korea.
11Department of Biomedical Engineering, Gachon University, Seongnam, Republic of Korea
12Department of Electrical and Computer Engineering, Yokohama National University Yokohama 240-8501, Japan.
13Department of Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
14Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, School of Biomedical Engineering, National Center for Translational Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, 200240, Shanghai, China; World Laureates Association (WLA) Laboratories, 201203, Shanghai, China.
15Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Seoul National University, Seoul 08826, Republic of Korea. Advanced Institutes of Convergence Technology, Suwon-si, Gyeonggi-do, Republic of Korea.
16Hypoxia/Ischemia Disease Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea. Advanced Institute of Convergence Technology, Seoul National University, Suwon16229, Republic of Korea.
*Equally contributing first authors.
#Equally contributing co-corresponding authors.
Corresponding authors: Diashun Ling Ph. D., Yuanzhe Piao Ph. D., Sun Ha Paek MD, Ph. D. (Main corresponding author)
Abstract
Superparamagnetic iron oxide nanoparticles (SPIONs) are promising contrast agents for imaging-guided cancer therapies. However, challenges such as the requirement for a high alternating magnetic field (AMF), dosage limitations, and suboptimal imaging contrast have hindered their practical applications.
Methods: First, the optimal doping ratio of Mn and Zn in MnxZn1-xFe2O4 nanoparticles synthesized using a modified high-temperature thermal decomposition method (mHTTD) was determined. Then, the magnetic and physical properties of the optimal 7-nm Mn0.5Zn0.5Fe2O4 SPIONs were systematically and comprehensively characterized via hysteresis measurements, dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray absorption fine structure (XAFS) spectroscopy, and X-ray absorption near edge structure (XANES) spectroscopy. Next, the stability, biosafety, biocompatibility, and theranostic performance of 7-nm Mn0.5Zn0.5Fe2O4 SPIONs in magnetic hyperthermia therapy (MHT) were evaluated by in vivo and in vitro studies involving mouse models, magnetic resonance imaging (MRI), and bioassays. The results were then compared with those for conventional SPIONs.
Results: Under an AMF of 140 Oe at 100 kHz, 7-nm Mn0.5Zn0.5Fe2O4 SPIONs demonstrated significantly higher heat production than conventional SPIONs. Following surface modification with methoxy-PEG-silane, PEGylated 7-nm Mn0.5Zn0.5Fe2O4 SPIONs showed excellent monodispersity and magnetic properties, with an exceptionally high T2 relaxivity (r2).
Conclusions: The high in vitro and in vivo theranostic performance of PEGylated 7-nm Mn0.5Zn0.5Fe2O4 SPIONs as efficient and stable contrast agents for treating glioblastoma, encompassing strengthened magnetic hyperthermia, activated anti-tumor immunity, and remarkable T2 contrast enhancement, underscores the potential of precisely designed ferrites to concurrently enhance the T2 contrast and magnetocaloric properties for optimal theranostic outcomes. Our study provides a compelling rationale for the development of tailored magnetic nanoprobes for improved glioblastoma theranostics.
논문정보
- Research article
- 2025년 02월 (BRIC 등록일 2025-03-18)
- 국내(교신)+국외 연구진
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