Ma Huan, Ye Tianzhen, Qu Guofeng, Qin Yilin, Liao Jiali, Yang Yuanyou, Zhang Wei, Liu Ning, Li Feize
Department of Nuclear Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, P. R. China.
Key Laboratory of Radiation Physics and Technology of the Ministry of Education, Institute of Nuclear Science and Technology, Sichuan University, Chengdu, 610064, P. R. China.
Sci Rep. 2025 May 25;15(1):18248. doi: 10.1038/s41598-025-03356-2.
Glioblastoma is the most common and aggressive tumor of the central nervous system. Locoregional administration of therapeutic radiopharmaceuticals appears to be a promising modality for recurrent glioblastomas. In this study, fibroblast activation protein alpha (FAPα) targeting molecule fibroblast activation protein inhibitor-04 (FAPI-04) was conjugated to polydopamine (PDA) nanoparticles, and then, α-emitter astatine-211 was labeled onto the nanocomposite to form [At]At-PDA-FAPI. In vitro, [At]At-PDA-FAPI was able to significantly reduce the cell viability, induce DSB formation, arrest cell cycle at G2/M phase and promote cell apoptosis. Furthermore, [At]At-PDA-FAPI exhibited effective tumor inhibition ability in U87MG xenografts. Mice received 0.56 MBq [At]At-PDA-FAPI showed a reduced tumor volume of approximately 65% on the 9th day after injection, and the median survival in this group (48 days) was obviously improved compared with that in the saline group (18 days). Meanwhile, increased apoptosis was also observed in tumor sites after [At]At-PDA-FAPI treatment. In addition, H&E analysis of major organs confirmed the biological safety of [At]At-PDA-FAPI. This study provides an effective and promising strategy for locoregional treatment of glioblastoma.
胶质母细胞瘤是中枢神经系统最常见且侵袭性最强的肿瘤。治疗性放射性药物的局部给药似乎是复发性胶质母细胞瘤的一种有前景的治疗方式。在本研究中，将靶向成纤维细胞活化蛋白α（FAPα）的分子成纤维细胞活化蛋白抑制剂-04（FAPI-04）与聚多巴胺（PDA）纳米颗粒偶联，然后将α发射体砹-211标记到该纳米复合材料上，形成[At]At-PDA-FAPI。在体外，[At]At-PDA-FAPI能够显著降低细胞活力、诱导双链断裂（DSB）形成、使细胞周期停滞在G2/M期并促进细胞凋亡。此外，[At]At-PDA-FAPI在U87MG异种移植瘤中表现出有效的肿瘤抑制能力。接受0.56 MBq [At]At-PDA-FAPI的小鼠在注射后第9天肿瘤体积减少了约65%，该组的中位生存期（48天）与生理盐水组（18天）相比明显延长。同时，[At]At-PDA-FAPI治疗后在肿瘤部位也观察到凋亡增加。此外，对主要器官的苏木精-伊红（H&E）分析证实了[At]At-PDA-FAPI的生物安全性。本研究为胶质母细胞瘤的局部治疗提供了一种有效且有前景的策略。
