间充质干细胞
抗辐射性
癌症研究
胶质瘤
放射治疗
巨噬细胞
上皮-间质转换
转分化
肿瘤微环境
材料科学
胶质母细胞瘤
干细胞
下调和上调
生物
医学
细胞生物学
内科学
肿瘤细胞
体外
生物化学
基因
作者
Ruiqi Li,Lian Chen,Qin Ji,Qing Liang,Ying Zhu,Wei Fu,Tianyou Chen,Hongwei Duan,Wenshan He,Zushun Xu,Xiaofang Dai,Jinghua Ren
标识
DOI:10.1002/adfm.202213292
摘要
Abstract 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‐ κ B‐dependent manner. Hence, rationally designed macrophage membrane‐coated porous mesoporous silica nanoparticles (MMNs) in which therapeutic anti‐NF‐ κ B 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.
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