2025-04-03 京都府立医科大学
<関連情報>
- https://www.kpu-m.ac.jp/doc/news/2025/20250403.html
- https://www.kpu-m.ac.jp/doc/news/2025/files/38288.pdf
- https://pubs.acs.org/doi/10.1021/acsnano.4c06753
2-ニトロイミダゾール誘導体で修飾した超常磁性酸化鉄ナノ粒子は膠芽腫の低酸素領域を描出し放射線治療効果を向上させる 2-Nitroimidazole-Functionalized Superparamagnetic Iron Oxide Nanoparticles Detect Hypoxic Regions of Glioblastomas on MRI and Improve Radiotherapy Efficacy
Yuki Yoshino,Fumi Yoshino,Ichio Aoki,Yasuyuki Mori,Gen Suzuki,Shunichiro Tsuji,Tsukuru Amano,Akihiko Shiino,Tokuhiro Chano,Yoshio Furusho,Takashi Murakami,Hideya Yamazaki,and Kei Yamada
ACS nano Published: March 26, 2025
DOI:https://doi.org/10.1021/acsnano.4c06753
Abstract
The presence of hypoxic regions in tumors is associated with malignancy and is an important target for the high-precision diagnosis and treatment of tumors. Radioresistant hypoxic regions can be precisely identified and treated without the use of high doses of radiation if hypoxic region-specific contrast agents have a therapeutic effect. In this study, we synthesized a therapeutic-diagnostic complex agent (SPION-PG-NI) by combining polyglycerol-functionalized superparamagnetic iron oxide nanoparticles (SPION-PG, core diameter of 8.8 ± 1.9 nm) as an MRI contrast agent and 2-nitroimidazole (NI, a pimonidazole derivative) as a hypoxia-targeted ligand to visually evaluate hypoxic regions using MRI and improve radiotherapy efficacy at those sites. SPION-PG-NI showed a concentration-dependent contrast effect and had significantly higher accumulation in subcutaneous glioblastomas than the control agent, SPION-PG, 24 h after administration. Immunohistological evaluations showed that the SPION-PG-NI-accumulated regions corresponded well to hypoxic regions. SPION-PG-NI showed neither migration into the brain parenchyma nor neurotoxicity. Both SPION-PG and SPION-PG-NI decrease reactive oxygen species (ROS); however, they improve radiotherapy efficacy in hypoxic glioblastoma cells due to cytotoxicity. This effect of SPION-PG-NI was significantly higher than that of SPION-PG (p < 0.01). After 12 Gy irradiation, the mean normalized glioblastoma tumor volume on day 38 in the SPION-PG-NI group (288%) was significantly lower than that in the control group (882%) (p < 0.05). Collectively, these findings suggest the potential of SPION-PG-NI as a useful and safe tumor theranostic nanodevice for hypoxic imaging and improving radiotherapy efficacy.
