替莫唑胺
癌症研究
肿瘤微环境
免疫系统
基因沉默
胶质母细胞瘤
脑瘤
血脑屏障
生物
材料科学
RNA干扰
胶质瘤
医学
中枢神经系统
免疫学
神经科学
病理
基因
生物化学
核糖核酸
作者
Chen-Meng Qiao,Jun Yang,Qi Shen,Ruiyuan Liu,Yanhui Li,Yuanjie Shi,Jingli Chen,Yan‐Qin Shen,Zhubing Xiao,Jie Weng,Xin Zhang
标识
DOI:10.1002/adma.201705054
摘要
The chemotherapy of glioblastoma is severely hindered by the immunosuppressive tumor microenvironment, especially the tumor growth factor β (TGF-β), an immunosuppressive cytokine. In this study, it is proposed to employ RNAi-based immunomodulation to modify the tumor immune microenvironment and improve the effect of chemotherapy. Herein, a nanotheranostic system (Angiopep LipoPCB(Temozolomide+BAP/siTGF-β), ALBTA) with dual targeting and ROS response is established for intracranial glioblastoma treatment. The traceable nanoparticles exhibit strong siRNA condensation, high drug loading efficiency, good serum stability, and magnetic property. They can efficiently cross the blood-brain barrier and target to glioblastoma cells via receptor-mediated transcytosis. The zwitterionic lipid (distearoyl phosphoethanol-amine-polycarboxybetaine lipid) in ALBTA promotes endosomal/lysosomal escape, and thus enhances the cytotoxicity of temozolomide and improves gene silencing efficiency of siTGF-β. ALBTA significantly improves the immunosuppressive microenvironment and prolongs the survival time of glioma-bearing mice. Moreover, ALBTA can be accurately traced by MRI in brain tumors. The study indicates that this immunochemotherapeutic platform can serve as a flexible and powerful synergistic system for treatment with brain tumors as well as other brain diseases in central nervous system.
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