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Outline
The treatment of gliomas faces significant challenges due to limitations imposed by the blood-brain barrier and the immunosuppressive tumor microenvironment. This study developed a perillyl alcohol-based nanoemulsion (POH-NE), which utilizes the reversible BBB-opening property of POH to efficiently deliver the STING agonist MSA-2 into the brain, aiming to achieve synergistic immunomodulation and antitumor therapy. MSA-2POH-NE exhibits uniform particle size (87.6 ± 2.3 nm) and neutral surface charge (-0.17 ± 0.1 mV), demonstrating system stability. In vivo distribution experiments demonstrated that POH-NE increased drug accumulation in the brain to 4.6 times that of conventional nanoemulsions. Mechanistic studies revealed that POH-NE reversibly reduced transendothelial electrical resistance and downregulated the expression of tight junction proteins Claudin-5 and ZO-1, while exerting no significant effect on the non-tight junction protein CD31. This suggests that POH may facilitate controllable BBB opening through coordinated paracellular and transcellular pathways. In an orthotopic glioma model, MSA-2POH-NE significantly activated the STING signaling pathway, promoted type I interferon production, enhanced the infiltration and activation of dendritic cells and cytotoxic T lymphocytes within tumors, and cooperatively reversed the immunosuppressive microenvironment. All animal experiments had been approved by the Experimental Animal Ethics Committee of the Institute of Laboratory Animals Science, Chinese Academy of Medical Sciences (No: SXD23001). In conclusion, this study proposed a novel combinatorial strategy for glioma immunotherapy based on reversible BBB opening and STING pathway activation, providing an experimental foundation for subsequent translational research.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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