Premium
Traceable Nanoparticles with Dual Targeting and ROS Response for RNAi‐Based Immunochemotherapy of Intracranial Glioblastoma Treatment
Author(s) -
Qiao Chenmeng,
Yang Jun,
Shen Qi,
Liu Ruiyuan,
Li Yanhui,
Shi Yuanjie,
Chen Jingli,
Shen Yanqin,
Xiao Zuobing,
Weng Jie,
Zhang Xin
Publication year - 2018
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.201705054
Subject(s) - temozolomide , cancer research , tumor microenvironment , glioma , immune system , gene silencing , brain tumor , rna interference , glioblastoma , blood–brain barrier , materials science , biology , central nervous system , immunology , medicine , pathology , neuroscience , gene , biochemistry , rna
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.