Traceable Nanoparticles with Dual Targeting and ROS Response for RNAi-Based Immunochemotherapy of Intracranial Glioblastoma Treatment
Traceable Nanoparticles with Dual Targeting and ROS Response for RNAi-Based Immunochemotherapy of Intracranial Glioblastoma Treatment
复制标题
具有双重靶向和 ROS 反应的可追踪纳米颗粒用于基于 RNAi 的颅内胶质母细胞瘤免疫化疗治疗
DOI：
10.1002/adma.201705054
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发表时间：
2018-05-03
影响因子：
29.4
通讯作者：
Zhang, Xin
中科院分区：
文献类型：
--
作者：
Qiao, Chenmeng;Yang, Jun;Zhang, Xin
胶质母细胞瘤的化疗受到免疫抑制性肿瘤微环境的严重阻碍，尤其是免疫抑制性细胞因子肿瘤生长因子β（TGF-β）。本研究提出采用基于RNAi的免疫调节来改变肿瘤免疫微环境，提高化疗效果。在此，建立了具有双重靶向和ROS响应的纳米治疗系统（Angiopep LipoPCB（替莫唑胺+BAP/siTGF-β），ALBTA）用于颅内胶质母细胞瘤的治疗。可追踪的纳米粒子表现出强的siRNA凝聚、高载药效率、良好的血清稳定性和磁性。它们可以有效地穿过血脑屏障，并通过受体介导的转胞吞作用靶向胶质母细胞瘤细胞。 ALBTA中的两性离子脂质（二硬脂酰磷酸乙醇-胺-聚羧基甜菜碱脂质）促进内体/溶酶体逃逸，从而增强替莫唑胺的细胞毒性并提高siTGF-β基因沉默效率，ALBTA显着改善免疫抑制微环境，延长胶质瘤小鼠的生存时间。此外，脑肿瘤中的 ALBTA 可以通过 MRI 准确追踪。研究表明，该免疫化疗平台可以作为灵活而强大的协同系统，用于治疗脑肿瘤以及中枢神经系统的其他脑部疾病。
The chemotherapy of glioblastoma is severely hindered by the immunosuppressive tumor microenvironment, especially the tumor growth factor beta (TGF-beta), 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-beta), 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-beta 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.