Macrophage membrane-coated nanoparticles sensitize glioblastoma to radiation by suppressing proneural–mesenchymal transformation in glioma stem cells

Radiotherapy is identified as a crucial treatment for patients with glioblastoma, but recurrence is inevitable. The efficacy of radiotherapy is severely hampered partially due to the tumor evolution. Growing evidence suggests that proneural glioma stem cells can acquire mesenchymal features coupled...

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Main Authors: Li, Ruiqi, Chen, Lian, Ji, Qin, Liang, Qing, Zhu, Ying, Fu, Wei, Chen, Tianyou, Duan, Hongwei, He, Wenshan, Xu, Zushun, Dai, Xiaofang, Ren, Jinghua
Other Authors: School of Chemical and Biomedical Engineering
Format: Article
Language:English
Published: 2023
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Online Access:https://hdl.handle.net/10356/170643
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1706432023-09-25T02:56:08Z Macrophage membrane-coated nanoparticles sensitize glioblastoma to radiation by suppressing proneural–mesenchymal transformation in glioma stem cells Li, Ruiqi Chen, Lian Ji, Qin Liang, Qing Zhu, Ying Fu, Wei Chen, Tianyou Duan, Hongwei He, Wenshan Xu, Zushun Dai, Xiaofang Ren, Jinghua School of Chemical and Biomedical Engineering Engineering::Chemical engineering Glioblastoma Glioma Stem Cells Radiotherapy is identified as a crucial treatment for patients with glioblastoma, but recurrence is inevitable. The efficacy of radiotherapy is severely hampered partially due to the tumor evolution. Growing evidence suggests that proneural glioma stem cells can acquire mesenchymal features coupled with increased radioresistance. Thus, a better understanding of mechanisms underlying tumor subclonal evolution may develop new strategies. Herein, data highlighting a positive correlation between the accumulation of macrophage in the glioblastoma microenvironment after irradiation and mesenchymal transdifferentiation in glioblastoma are presented. Mechanistically, elevated production of inflammatory cytokines released by macrophages promotes mesenchymal transition in an NF-κB-dependent manner. Hence, rationally designed macrophage membrane-coated porous mesoporous silica nanoparticles (MMNs) in which therapeutic anti-NF-κB peptides are loaded for enhancing radiotherapy of glioblastoma are constructed. The combination of MMNs and fractionated irradiation results in the blockage of tumor evolution and therapy resistance in glioblastoma-bearing mice. Intriguingly, the macrophage invasion across the blood-brain barrier is inhibited competitively by MMNs, suggesting that these nanoparticles can fundamentally halt the evolution of radioresistant clones. Taken together, the biomimetic MMNs represent a promising strategy that prevents mesenchymal transition and improves therapeutic response to irradiation as well as overall survival in patients with glioblastoma. This work was supported by National Natural Science Foundation of China (Nos. 82072944, 82072800, and 81874084), Natural Science Foundation of Hubei Province (No. 2020CFB786), and Science, Technology and Innovation Commission of Shenzhen Municipality (JCYJ20210324141802006). 2023-09-25T02:56:08Z 2023-09-25T02:56:08Z 2023 Journal Article Li, R., Chen, L., Ji, Q., Liang, Q., Zhu, Y., Fu, W., Chen, T., Duan, H., He, W., Xu, Z., Dai, X. & Ren, J. (2023). Macrophage membrane-coated nanoparticles sensitize glioblastoma to radiation by suppressing proneural–mesenchymal transformation in glioma stem cells. Advanced Functional Materials, 33(37), 2213292-. https://dx.doi.org/10.1002/adfm.202213292 1616-301X https://hdl.handle.net/10356/170643 10.1002/adfm.202213292 2-s2.0-85162074007 37 33 2213292 en Advanced Functional Materials © 2023 Wiley-VCH GmbH. All rights reserved.
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Engineering::Chemical engineering
Glioblastoma
Glioma Stem Cells
spellingShingle Engineering::Chemical engineering
Glioblastoma
Glioma Stem Cells
Li, Ruiqi
Chen, Lian
Ji, Qin
Liang, Qing
Zhu, Ying
Fu, Wei
Chen, Tianyou
Duan, Hongwei
He, Wenshan
Xu, Zushun
Dai, Xiaofang
Ren, Jinghua
Macrophage membrane-coated nanoparticles sensitize glioblastoma to radiation by suppressing proneural–mesenchymal transformation in glioma stem cells
description Radiotherapy is identified as a crucial treatment for patients with glioblastoma, but recurrence is inevitable. The efficacy of radiotherapy is severely hampered partially due to the tumor evolution. Growing evidence suggests that proneural glioma stem cells can acquire mesenchymal features coupled with increased radioresistance. Thus, a better understanding of mechanisms underlying tumor subclonal evolution may develop new strategies. Herein, data highlighting a positive correlation between the accumulation of macrophage in the glioblastoma microenvironment after irradiation and mesenchymal transdifferentiation in glioblastoma are presented. Mechanistically, elevated production of inflammatory cytokines released by macrophages promotes mesenchymal transition in an NF-κB-dependent manner. Hence, rationally designed macrophage membrane-coated porous mesoporous silica nanoparticles (MMNs) in which therapeutic anti-NF-κB peptides are loaded for enhancing radiotherapy of glioblastoma are constructed. The combination of MMNs and fractionated irradiation results in the blockage of tumor evolution and therapy resistance in glioblastoma-bearing mice. Intriguingly, the macrophage invasion across the blood-brain barrier is inhibited competitively by MMNs, suggesting that these nanoparticles can fundamentally halt the evolution of radioresistant clones. Taken together, the biomimetic MMNs represent a promising strategy that prevents mesenchymal transition and improves therapeutic response to irradiation as well as overall survival in patients with glioblastoma.
author2 School of Chemical and Biomedical Engineering
author_facet School of Chemical and Biomedical Engineering
Li, Ruiqi
Chen, Lian
Ji, Qin
Liang, Qing
Zhu, Ying
Fu, Wei
Chen, Tianyou
Duan, Hongwei
He, Wenshan
Xu, Zushun
Dai, Xiaofang
Ren, Jinghua
format Article
author Li, Ruiqi
Chen, Lian
Ji, Qin
Liang, Qing
Zhu, Ying
Fu, Wei
Chen, Tianyou
Duan, Hongwei
He, Wenshan
Xu, Zushun
Dai, Xiaofang
Ren, Jinghua
author_sort Li, Ruiqi
title Macrophage membrane-coated nanoparticles sensitize glioblastoma to radiation by suppressing proneural–mesenchymal transformation in glioma stem cells
title_short Macrophage membrane-coated nanoparticles sensitize glioblastoma to radiation by suppressing proneural–mesenchymal transformation in glioma stem cells
title_full Macrophage membrane-coated nanoparticles sensitize glioblastoma to radiation by suppressing proneural–mesenchymal transformation in glioma stem cells
title_fullStr Macrophage membrane-coated nanoparticles sensitize glioblastoma to radiation by suppressing proneural–mesenchymal transformation in glioma stem cells
title_full_unstemmed Macrophage membrane-coated nanoparticles sensitize glioblastoma to radiation by suppressing proneural–mesenchymal transformation in glioma stem cells
title_sort macrophage membrane-coated nanoparticles sensitize glioblastoma to radiation by suppressing proneural–mesenchymal transformation in glioma stem cells
publishDate 2023
url https://hdl.handle.net/10356/170643
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