Low-dose pleiotropic radiosensitive nanoformulations for three-pronged radiochemotherapy of hypoxic brain glioblastoma under BOLD/DWI monitoring
Abstract Background Hypoxia-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 a...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Cancer Nanotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12645-023-00159-w |
| _version_ | 1811171835511832576 |
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| author | Fangshi Zhao Xiaoyi Wang Wei Zhu Dongju Zhao Caihua Ye Yanyan Guo Yan Dou |
| author_facet | Fangshi Zhao Xiaoyi Wang Wei Zhu Dongju Zhao Caihua Ye Yanyan Guo Yan Dou |
| author_sort | Fangshi Zhao |
| collection | DOAJ |
| description | Abstract Background Hypoxia-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. Results Herein, 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. Conclusions This work provides a promising alternative for hypoxia-specific GBM-targeted comprehensive therapy, noninvasive monitoring, and precise prognosis. Graphical Abstract |
| first_indexed | 2024-04-10T17:21:50Z |
| format | Article |
| id | doaj.art-9d87a76a90114dd7b30053da588415aa |
| institution | Directory Open Access Journal |
| issn | 1868-6958 1868-6966 |
| language | English |
| last_indexed | 2024-04-10T17:21:50Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Nanotechnology |
| spelling | doaj.art-9d87a76a90114dd7b30053da588415aa2023-02-05T12:04:50ZengBMCCancer Nanotechnology1868-69581868-69662023-02-0114112210.1186/s12645-023-00159-wLow-dose pleiotropic radiosensitive nanoformulations for three-pronged radiochemotherapy of hypoxic brain glioblastoma under BOLD/DWI monitoringFangshi Zhao0Xiaoyi Wang1Wei Zhu2Dongju Zhao3Caihua Ye4Yanyan Guo5Yan Dou6Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General HospitalDepartment of Ultrasound and Department of Radiation Oncology, The Second Hospital of Tianjin Medical UniversityTianjin Huanhu HospitalDepartment of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General HospitalDepartment of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General HospitalDepartment of Ultrasound and Department of Radiation Oncology, The Second Hospital of Tianjin Medical UniversityDepartment of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General HospitalAbstract Background Hypoxia-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. Results Herein, 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. Conclusions This work provides a promising alternative for hypoxia-specific GBM-targeted comprehensive therapy, noninvasive monitoring, and precise prognosis. Graphical Abstracthttps://doi.org/10.1186/s12645-023-00159-wNanomedicineGlioblastomaTumor hypoxiaRadiochemotherapyHypoxia-activated therapyNitric oxide |
| spellingShingle | Fangshi Zhao Xiaoyi Wang Wei Zhu Dongju Zhao Caihua Ye Yanyan Guo Yan Dou Low-dose pleiotropic radiosensitive nanoformulations for three-pronged radiochemotherapy of hypoxic brain glioblastoma under BOLD/DWI monitoring Cancer Nanotechnology Nanomedicine Glioblastoma Tumor hypoxia Radiochemotherapy Hypoxia-activated therapy Nitric oxide |
| title | Low-dose pleiotropic radiosensitive nanoformulations for three-pronged radiochemotherapy of hypoxic brain glioblastoma under BOLD/DWI monitoring |
| title_full | Low-dose pleiotropic radiosensitive nanoformulations for three-pronged radiochemotherapy of hypoxic brain glioblastoma under BOLD/DWI monitoring |
| title_fullStr | Low-dose pleiotropic radiosensitive nanoformulations for three-pronged radiochemotherapy of hypoxic brain glioblastoma under BOLD/DWI monitoring |
| title_full_unstemmed | Low-dose pleiotropic radiosensitive nanoformulations for three-pronged radiochemotherapy of hypoxic brain glioblastoma under BOLD/DWI monitoring |
| title_short | Low-dose pleiotropic radiosensitive nanoformulations for three-pronged radiochemotherapy of hypoxic brain glioblastoma under BOLD/DWI monitoring |
| title_sort | low dose pleiotropic radiosensitive nanoformulations for three pronged radiochemotherapy of hypoxic brain glioblastoma under bold dwi monitoring |
| topic | Nanomedicine Glioblastoma Tumor hypoxia Radiochemotherapy Hypoxia-activated therapy Nitric oxide |
| url | https://doi.org/10.1186/s12645-023-00159-w |
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