Mitophagy-mediated inhibition of glioma proliferation by cannabidiol-loaded hybrid exosomal vesicles
10.11665/j.issn.1000-5048.2025120401
- VernacularTitle:融合外泌体囊泡负载大麻二酚通过线粒体自噬抑制胶质瘤增殖
- Author:
Wenhui HAN
1
;
Yan SHEN
;
Daquan CHEN
;
Ji LIU
Author Information
1. 烟台大学药学院, 烟台264005;中国药科大学药学院, 南京211198
- Publication Type:Journal Article
- Keywords:
hybrid exosomal vesicles;
targeted therapy;
cannabidiol;
mitophagy;
glioblastoma
- From:
Journal of China Pharmaceutical University
2026;57(4):466-478
- CountryChina
- Language:Chinese
-
Abstract:
This study aimed to investigate the use of hybrid exosomal vesicles (RU-exos), prepared by fusing exosomes derived from U87 and RAW264.7 cells, as a delivery system for cannabidiol (CBD) to cross the blood–brain barrier (BBB) and target glioblastoma (GBM), thereby exerting antitumor effects through the regulation of mitophagy. The RU-exos@CBD formulation was characterized using transmission electron microscopy, dynamic light scattering, and zeta potential measurements. Intracellular reactive oxygen species (ROS) levels were measured using the DCFH-DA probe, changes in mitochondrial membrane potential (MMP) were assessed using the JC-1 probe, and the expression of mitophagy-related proteins was analyzed by Western blotting. In addition, an intracranial orthotopic GBM model was established in nude mice to evaluate the in vivo targeting ability, therapeutic efficacy, and biosafety of RU-exos@CBD. Immunohistochemistry (IHC) and immunofluorescence (IF) staining were performed to assess tumor cell proliferation. The results showed that RU-exos@CBD treatment induced intracellular ROS accumulation and decreased MMP, providing preliminary evidence for the induction of mitophagy. Further mechanistic studies demonstrated that RU-exos@CBD activated mitophagy by inhibiting the PI3K/AKT/mTOR signaling pathway. In vivoexperiments confirmed that RU-exos@CBD effectively crossed the BBB and accumulated in tumor regions. Compared with free CBD, RU-exos@CBD significantly enhanced the inhibition of GBM proliferation. Hematoxylin and eosin (H&E) staining of major organs revealed no apparent pathological damage, indicating that RU-exos@CBD exhibited favorable biosafety and tissue compatibility.
