The major challenges of immunotherapy for glioblastoma are that drugs cannot target tumor sites accurately and properly activate complex immune responses. Herein, we design and prepare a kind of chemotactic nanomotor loaded with brain endothelial cell targeting agent angiopep-2 and anti-tumor drug (Lonidamine modified with mitochondrial targeting agent triphenylphosphine, TLND). Reactive oxygen species and inducible nitric oxide synthase (ROS/iNOS), which are specifically highly expressed in glioblastoma microenvironment, are used as chemoattractants to induce the chemotactic behavior of the nanomotors. We propose a precise targeting strategy of brain endothelial cells-tumor cells-mitochondria. Results verified that the released NO and TLND can regulate the immune circulation through multiple steps to enhance the effect of immunotherapy, including triggering the immunogenic cell death of tumor, inducing dendritic cells to mature, promoting cytotoxic T cells infiltration, and regulating tumor microenvironment. Moreover, this treatment strategy can form an effective immune memory effect to prevent tumor metastasis and recurrence.

胶质母细胞瘤免疫治疗的主要挑战是药物不能准确靶向肿瘤部位并正确激活复杂的免疫反应。在此，我们设计并制备了一种负载脑内皮细胞靶向剂 angiopep-2 和抗肿瘤药物（线粒体靶向剂三苯基膦修饰的 Lonidamine，TLND）的趋化纳米马达。在胶质母细胞瘤微环境中特异性高表达的活性氧和诱导型一氧化氮合酶 (ROS/iNOS) 被用作化学引诱剂来诱导纳米马达的趋化行为。我们提出了脑内皮细胞-肿瘤细胞-线粒体的精确靶向策略。结果证实，释放的NO和TLND可通过多步调节免疫循环，增强免疫治疗效果，包括触发肿瘤免疫原性细胞死亡、诱导树突状细胞成熟、促进细胞毒性T细胞浸润、调节肿瘤微环境等。而且，这种治疗策略可以形成有效的免疫记忆效应，防止肿瘤转移和复发。