Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma
Abstract Although RNA interference (RNAi) therapy has emerged as a potential tool in cancer therapeutics, the application of RNAi to glioblastoma (GBM) remains a hurdle. Herein, to improve the therapeutic effect of RNAi on GBM, a cancer cell membrane (CCM)-disguised hypoxia-triggered RNAi nanomedici...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-023-01960-w |
| _version_ | 1797784434517213184 |
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| author | Zhen Wang Xiang-long Tang Meng-jie Zhao Yi-ding Zhang Yong Xiao Yu-yang Liu Chun-fa Qian Yan-dong Xie Yong Liu Yuan-jie Zou Kun Yang Hong-yi Liu |
| author_facet | Zhen Wang Xiang-long Tang Meng-jie Zhao Yi-ding Zhang Yong Xiao Yu-yang Liu Chun-fa Qian Yan-dong Xie Yong Liu Yuan-jie Zou Kun Yang Hong-yi Liu |
| author_sort | Zhen Wang |
| collection | DOAJ |
| description | Abstract Although RNA interference (RNAi) therapy has emerged as a potential tool in cancer therapeutics, the application of RNAi to glioblastoma (GBM) remains a hurdle. Herein, to improve the therapeutic effect of RNAi on GBM, a cancer cell membrane (CCM)-disguised hypoxia-triggered RNAi nanomedicine was developed for short interfering RNA (siRNA) delivery to sensitize cells to chemotherapy and radiotherapy. Our synthesized CCM-disguised RNAi nanomedicine showed prolonged blood circulation, high BBB transcytosis and specific accumulation in GBM sites via homotypic recognition. Disruption and effective anti-GBM agents were triggered in the hypoxic region, leading to efficient tumor suppression by using phosphoglycerate kinase 1 (PGK1) silencing to enhance paclitaxel-induced chemotherapy and sensitize hypoxic GBM cells to ionizing radiation. In summary, a biomimetic intelligent RNAi nanomedicine has been developed for siRNA delivery to synergistically mediate a combined chemo/radiotherapy that presents immune-free and hypoxia-triggered properties with high survival rates for orthotopic GBM treatment. Graphical Abstract |
| first_indexed | 2024-03-13T00:39:50Z |
| format | Article |
| id | doaj.art-92c2b613582e4d609a73b0d1c88e8718 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-03-13T00:39:50Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-92c2b613582e4d609a73b0d1c88e87182023-07-09T11:23:35ZengBMCJournal of Nanobiotechnology1477-31552023-07-0121111810.1186/s12951-023-01960-wBiomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastomaZhen Wang0Xiang-long Tang1Meng-jie Zhao2Yi-ding Zhang3Yong Xiao4Yu-yang Liu5Chun-fa Qian6Yan-dong Xie7Yong Liu8Yuan-jie Zou9Kun Yang10Hong-yi Liu11Department of Neurosurgery, The Affiliated Brain Hospital With Nanjing Medical University, Fourth Clinical College of Nanjing Medical UniversityDepartment of Neuro-Psychiatric Institute, The Affiliated Brain Hospital With Nanjing Medical UniversityDepartment of Neuro-Psychiatric Institute, The Affiliated Brain Hospital With Nanjing Medical UniversityDepartment of Neurosurgery, The Affiliated Brain Hospital With Nanjing Medical University, Fourth Clinical College of Nanjing Medical UniversityDepartment of Neurosurgery, The Affiliated Brain Hospital With Nanjing Medical University, Fourth Clinical College of Nanjing Medical UniversityDepartment of Neurosurgery, The Affiliated Brain Hospital With Nanjing Medical University, Fourth Clinical College of Nanjing Medical UniversityDepartment of Neurosurgery, The Affiliated Brain Hospital With Nanjing Medical University, Fourth Clinical College of Nanjing Medical UniversityDepartment of Neurosurgery, The Affiliated Brain Hospital With Nanjing Medical University, Fourth Clinical College of Nanjing Medical UniversityDepartment of Neurosurgery, The Affiliated Brain Hospital With Nanjing Medical University, Fourth Clinical College of Nanjing Medical UniversityDepartment of Neurosurgery, The Affiliated Brain Hospital With Nanjing Medical University, Fourth Clinical College of Nanjing Medical UniversityDepartment of Neurosurgery, The Affiliated Brain Hospital With Nanjing Medical University, Fourth Clinical College of Nanjing Medical UniversityDepartment of Neurosurgery, The Affiliated Brain Hospital With Nanjing Medical University, Fourth Clinical College of Nanjing Medical UniversityAbstract Although RNA interference (RNAi) therapy has emerged as a potential tool in cancer therapeutics, the application of RNAi to glioblastoma (GBM) remains a hurdle. Herein, to improve the therapeutic effect of RNAi on GBM, a cancer cell membrane (CCM)-disguised hypoxia-triggered RNAi nanomedicine was developed for short interfering RNA (siRNA) delivery to sensitize cells to chemotherapy and radiotherapy. Our synthesized CCM-disguised RNAi nanomedicine showed prolonged blood circulation, high BBB transcytosis and specific accumulation in GBM sites via homotypic recognition. Disruption and effective anti-GBM agents were triggered in the hypoxic region, leading to efficient tumor suppression by using phosphoglycerate kinase 1 (PGK1) silencing to enhance paclitaxel-induced chemotherapy and sensitize hypoxic GBM cells to ionizing radiation. In summary, a biomimetic intelligent RNAi nanomedicine has been developed for siRNA delivery to synergistically mediate a combined chemo/radiotherapy that presents immune-free and hypoxia-triggered properties with high survival rates for orthotopic GBM treatment. Graphical Abstracthttps://doi.org/10.1186/s12951-023-01960-wCancer cell membraneHypoxia-triggeredChemotherapyRadiotherapysiRNA deliveryGlioblastoma |
| spellingShingle | Zhen Wang Xiang-long Tang Meng-jie Zhao Yi-ding Zhang Yong Xiao Yu-yang Liu Chun-fa Qian Yan-dong Xie Yong Liu Yuan-jie Zou Kun Yang Hong-yi Liu Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma Journal of Nanobiotechnology Cancer cell membrane Hypoxia-triggered Chemotherapy Radiotherapy siRNA delivery Glioblastoma |
| title | Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma |
| title_full | Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma |
| title_fullStr | Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma |
| title_full_unstemmed | Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma |
| title_short | Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma |
| title_sort | biomimetic hypoxia triggered rnai nanomedicine for synergistically mediating chemo radiotherapy of glioblastoma |
| topic | Cancer cell membrane Hypoxia-triggered Chemotherapy Radiotherapy siRNA delivery Glioblastoma |
| url | https://doi.org/10.1186/s12951-023-01960-w |
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