Yalamandala Bhanu Nirosha, Huynh Thi My Hue, Lien Hui-Wen, Pan Wan-Chi, Iao Hoi Man, Moorthy Thrinayan, Chang Yun-Hsuan, Hu Shang-Hsiu
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 300044, Hsinchu, Taiwan.
Drug Deliv Transl Res. 2025 Jan 9. doi: 10.1007/s13346-024-01778-5.
Glioblastoma (GBM), a highly aggressive brain tumor, poses significant treatment challenges due to its highly immunosuppressive microenvironment and the brain immune privilege. Immunotherapy activating the immune system and T lymphocyte infiltration holds great promise against GBM. However, the brain's low immunogenicity and the difficulty of crossing the blood-brain barrier (BBB) hinder therapeutic efficacy. Recent advancements in immune-actuated particles for targeted drug delivery have shown the potential to overcome these obstacles. These particles interact with the BBB by rapidly and reversibly disrupting its structure, thereby significantly enhancing targeting and penetrating delivery. The BBB targeting also minimizes potential long-term damage. At GBM, the particles demonstrated effective chemotherapy, chemodynamic therapy, photothermal therapy (PTT), photodynamic therapy (PDT), radiotherapy, or magnetotherapy, facilitating tumor disruption and promoting antigen release. Additionally, components of the delivery system retained autologous tumor-associated antigens and presented them to dendritic cells (DCs), ensuring prolonged immune activation. This review explores the immunosuppressive mechanisms of GBM, existing therapeutic strategies, and the role of nanomaterials in enhancing immunotherapy. We also discuss innovative particle-based approaches designed to traverse the BBB by mimicking innate immune functions to improve treatment outcomes for brain tumors.
胶质母细胞瘤（GBM）是一种极具侵袭性的脑肿瘤，因其高度免疫抑制的微环境和脑免疫特权而带来重大治疗挑战。激活免疫系统和T淋巴细胞浸润的免疫疗法对GBM具有巨大潜力。然而，脑的低免疫原性以及跨越血脑屏障（BBB）的困难阻碍了治疗效果。用于靶向药物递送的免疫驱动颗粒的最新进展已显示出克服这些障碍的潜力。这些颗粒通过快速且可逆地破坏血脑屏障的结构与其相互作用，从而显著增强靶向和穿透递送。血脑屏障靶向还可将潜在的长期损伤降至最低。在GBM中，这些颗粒展示出有效的化疗、化学动力疗法、光热疗法（PTT）、光动力疗法（PDT）、放射疗法或磁疗法，有助于肿瘤破坏并促进抗原释放。此外，递送系统的成分保留自体肿瘤相关抗原并将其呈递给树突状细胞（DC），确保长期免疫激活。本综述探讨了GBM的免疫抑制机制、现有治疗策略以及纳米材料在增强免疫疗法中的作用。我们还讨论了旨在通过模拟先天免疫功能跨越血脑屏障以改善脑肿瘤治疗结果的基于颗粒的创新方法。
