Immune Exosomes Loading Self-Assembled Nanomicelles Traverse the Blood–Brain Barrier for Chemo-immunotherapy against Glioblastoma

作者：Jiwei Cui, Xue Wang, Jinge Li, Anran Zhu, Yingjiang Du, Wei Zeng, Yumiao Guo, Liuqing Di, Ruoning Wang · 发表于：ACS Nano · 年份：2023 · DOI：10.1021/acsnano.2c10219 · 被引用次数：249 · 研究领域：Extracellular vesicles in disease、Nanoplatforms for cancer theranostics、Nanoparticle-Based Drug Delivery

Effective drug delivery and prevention of postoperative recurrence are significant challenges for current glioblastoma (GBM) treatment. Poor drug delivery is mainly due to the presence of the blood-brain barrier (BBB), and postoperative recurrence is primarily due to the resistance of GBM cells to chemotherapeutic drugs and the presence of an immunosuppressive microenvironment. Herein, a biomimetic nanodrug delivery platform based on endogenous exosomes that could efficiently target the brain without targeting modifications and co-deliver pure drug nanomicelles and immune adjuvants for safe and efficient chemo-immunotherapy against GBM is prepared. Inspired by the self-assembly technology of small molecules, tanshinone IIA (TanIIA) and glycyrrhizic acid (GL), which are the inhibitors of signal transducers and activators of transcription 3 from traditional Chinese medicine (TCM), self-assembled to form TanIIA-GL nanomicelles (TGM). Endogenous serum exosomes are selected to coat the pure drug nanomicelles, and the CpG oligonucleotides, agonists of Toll-like receptor 9, are anchored on the exosome membrane to obtain immune exosomes loaded with TCM self-assembled nanomicelles (CpG-EXO/TGM). Our results demonstrate that CpG-EXO/TGM can bind free transferrin in blood, prolong blood circulation, and maintain intact structures when traversing the BBB and targeting GBM cells. In the GBM microenvironment, the strong anti-GBM effect of CpG-EXO/TGM is mainly attributed to two factors: (i...