Song Xiaowei, Xiao Liang, Xu Lingling, Jiang Yechun, Fu Wanyue, Chen Benjin, Zheng Wang, Qian Haisheng, Yu Yongqiang
Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei, Anhui 230022, P. R. China.
Research Center of Clinical Medical Imaging, Hefei, Anhui 230022, P. R. China.
ACS Appl Mater Interfaces. 2025 Apr 9;17(14):21478-21490. doi: 10.1021/acsami.5c01498. Epub 2025 Mar 27.
Radioresistance in tumors and the excess damage in normal tissues during radiotherapy (RT) restrict the clinical application of glioblastoma RT. Image-guided radiosensitization is hopefully adopted to achieve precision RT. Nevertheless, the therapeutic effect of radiosensitizers in glioblastoma is unsatisfactory due to limitations of the blood-brain barrier and poor tumor targeting. Herein, FeO@BiS nanoparticles coated with a glioblastoma cell membrane (denoted as FBM) have been designed to sensitize RT. FBM accumulates precisely within the tumors via external magnetism and homologous adhesion capability. Afterward, FBM releases high- atoms (Bismuth) in ionizing radiation and tumor micro acidic environments that interact with ionizing radiation to generate high densities of secondary radiation, which leads to enhanced radiation dose deposits. Simultaneously, FBM generates reactive oxygen species, accumulates lipid peroxidation and Fe, depletes glutathione, and downregulates glutathione peroxidase 4 to activate ferroptosis. Notably, the tumor growth inhibition rate of FBM-mediated RT via external magnetism increases to 75.49% in the orthotopic glioblastoma model. Besides, FBM with magnetic resonance imaging performance shows the potential application in tumor diagnosis and therapy surveillance, thereby reducing damage to adjacent normal tissues and realizing MRI-guided precision RT. Hence, the novel multifunctional nanoplatform offers the potential for image-guided radiosensitization induced by activating ferroptosis, thus presenting an efficient radiotherapeutic approach for glioblastoma.
肿瘤的放射抗性以及放疗（RT）期间正常组织中的过量损伤限制了胶质母细胞瘤放疗的临床应用。有望采用图像引导放射增敏来实现精确放疗。然而，由于血脑屏障的限制和肿瘤靶向性差，放射增敏剂在胶质母细胞瘤中的治疗效果并不理想。在此，设计了一种包被胶质母细胞瘤细胞膜的FeO@BiS纳米颗粒（记为FBM）来使放疗增敏。FBM通过外部磁性和同源粘附能力精确地在肿瘤内聚集。随后，FBM在电离辐射和肿瘤微酸性环境中释放高原子（铋），其与电离辐射相互作用产生高密度的次级辐射，从而导致辐射剂量沉积增加。同时，FBM产生活性氧，积累脂质过氧化和铁，消耗谷胱甘肽，并下调谷胱甘肽过氧化物酶4以激活铁死亡。值得注意的是，在原位胶质母细胞瘤模型中，通过外部磁性介导的FBM放疗的肿瘤生长抑制率提高到75.49%。此外，具有磁共振成像性能的FBM在肿瘤诊断和治疗监测中显示出潜在应用，从而减少对相邻正常组织的损伤并实现MRI引导的精确放疗。因此，这种新型多功能纳米平台为激活铁死亡诱导的图像引导放射增敏提供了潜力，从而为胶质母细胞瘤提供了一种有效的放射治疗方法。
