Glioblastoma, the most prevalent malignant brain tumor, is a lethal threat to human health, with aggressive and infiltrative growth characteristics that compromise the clinical treatment. Herein, we developed a vitamin D3-inserted lipid hybrid neutrophil membrane biomimetic multimodal nanoplatform (designated as NED@MnO₂-DOX) through doxorubicin (DOX)-loaded manganese dioxide nanoparticles (MnO₂) which were coated with a vitamin D₃-inserted lipid hybrid neutrophil membrane. It was demonstrated that in addition to chemotherapy and chemo-dynamic therapy efficacy, NED@MnO₂-DOX exhibited great power to activate and amplify immune responses related to the cGAS STING pathway, bolstering the secretion of type I interferon-β and proinflammatory cytokines, promoting the maturation of DC cells and infiltration of CD8⁺T cells into the glioma tissue, thereby reversing the immunosuppressive microenvironment of glioma from a “cold” tumor to a “hot” tumor. The biomimetic multimodal nanoplatform has potential as a multimodal strategy for glioma-targeted treatment, especially holding considerable promise for the development of innate immune therapy for glioma.

中文翻译：

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通过维生素 D3 插入的脂质杂交中性粒细胞膜仿生多模式纳米平台增强抗胶质瘤作用


胶质母细胞瘤是最常见的恶性脑肿瘤，对人类健康构成致命威胁，具有侵袭性和浸润性生长特征，影响临床治疗。在此，我们开发了一种通过载有阿霉素 （DOX） 的二氧化锰纳米颗粒 （MnO₂） 嵌入维生素 D 3 的脂质杂交中性粒细胞膜仿生多模式纳米平台（命名为 NED@MnO_2-DOX），该纳米颗粒包被了维生素 D₃ 插入的脂质杂交中性粒细胞膜。研究表明，除了化疗和化疗动态疗法的疗效外，NED@MnO 2-DOX 还表现出激活和放大与 cGAS STING 通路相关的免疫反应的巨大能力，增强 I 型干扰素β和促炎细胞因子的分泌，促进 DC 细胞的成熟和 CD8⁺ 的浸润T 细胞进入神经胶质瘤组织，从而将神经胶质瘤的免疫抑制微环境从“冷”肿瘤逆转为“热”肿瘤。仿生多模态纳米平台具有作为胶质瘤靶向治疗的多模态策略的潜力，尤其对胶质瘤先天免疫疗法的开发具有相当大的前景。