Low-dose pleiotropic radiosensitive nanoformulations for three-pronged radiochemotherapy of hypoxic brain glioblastoma under BOLD/DWI monitoring

Cancer Nanotechnology

Research

Dongju Zhao¹  Yan Dou¹  Fangshi Zhao¹  Caihua Ye¹  Xiaoyi Wang²  Yanyan Guo²  Wei Zhu³ 

[1] Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, 300052, Tianjin, China;Department of Ultrasound and Department of Radiation Oncology, The Second Hospital of Tianjin Medical University, 300211, Tianjin, China;Tianjin Huanhu Hospital, 300350, Tianjin, China;

关键词: Nanomedicine;    Glioblastoma;    Tumor hypoxia;    Radiochemotherapy;    Hypoxia-activated therapy;    Nitric oxide;    9.4 T BOLD/DWI imaging;   

DOI  :  10.1186/s12645-023-00159-w

 received in 2022-09-29, accepted in 2023-01-22,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundHypoxia-mediated radioresistance is the main obstacle to the successful treatment of glioblastoma (GBM). Enhancing hypoxic radiosensitivity and alleviating tumor hypoxia are both effective means to improve therapeutic efficacy, and the combination of the two is highly desirable and meaningful.ResultsHerein, we construct a low-dose pleiotropic radiosensitive nanoformulation consisting of a high-Z atomic nanocrystal core and mesoporous silica shell, surface-modified with angiopep-2 (ANG) peptide and loaded with nitric oxide (NO) donor and hypoxia-activated prodrug (AQ4N). Benefiting from ANG-mediated transcytosis, this nanoformulation can efficiently cross the BBB and accumulate preferentially in the brain. Low-dose radiation triggers this nanoformulation to exert a three-pronged synergistic therapeutic effect through high-Z-atom-dependent dose deposition enhancement, NO-mediated hypoxia relief, and AQ4N-induced hypoxia-selective killing, thereby significantly inhibiting GBM in situ growth while prolonging survival and maintaining stable body weight in the glioma-bearing mice. Meanwhile, the proposed in vivo 9.4 T BOLD/DWI can realize real-time dynamic assessment of local oxygen supply and radiosensitivity to monitor the therapeutic response of GBM.ConclusionsThis work provides a promising alternative for hypoxia-specific GBM-targeted comprehensive therapy, noninvasive monitoring, and precise prognosis.Graphical Abstract

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 3

Fig. 2

Fig. 1

Fig. 4

Fig. 2

Fig. 3

Fig. 1

Fig. 1

13731_2023_266_Article_IEq9.gif