抗坏血酸（AA）因其在 T 细胞依赖性抗肿瘤免疫中的新兴潜力而受到广泛关注。然而，过早的血液清除和免疫学“冷”肿瘤严重损害了其免疫治疗结果。因此，免疫抑制性肿瘤微环境（TME）的逆转是提高基于 AA 的免疫疗法有效性的前提，这取决于先进的 AA 递送和放大的免疫激活策略。在此，基于AA固定金属有机框架（MOF）的门控，精心设计了一种新型大肠杆菌（E. coli）外膜囊泡（OMV）-红细胞（RBC）混合膜（ERm）伪装的免疫调节纳米塔。 ）到负载硼替佐米（BTZ）的镁掺杂介孔二氧化硅（MMS）纳米载体上，可以通过化疗辅助抗坏血酸介导的免疫疗法（CAMIT）实现免疫景观重塑。一旦到达酸性 TME，纳米转塔内的酸敏感 MOF 看门人和 MMS 核心就会逐步降解，从而允许肿瘤选择性地顺序释放 AA 和 BTZ。释放的 BTZ 可以引起强烈的免疫原性细胞死亡 (ICD)，与 OMV 结合协同促进树突状细胞 (DC) 成熟，并最终与 Mg2 一起增加 T 细胞肿瘤浸润。 T细胞大军被AA进一步激活，表现出显着的抗肿瘤和抗转移性能。此外，CD8缺陷小鼠模型揭示了基于AA的CAMIT策略的T细胞依赖性免疫机制。除了提供多功能仿生混合纳米载体外，这项研究还有望建立一种基于多组件驱动纳米转塔的新免疫调节强化策略，用于高效 T 细胞激活增强协同 AA 免疫治疗。

Ascorbic acid (AA) has been attracting great attention with its emerging potential in T cell-dependent antitumor immunity. However, premature blood clearance and immunologically "cold" tumors severely compromise its immunotherapeutic outcomes. As such, the reversal of the immunosuppressive tumor microenvironment (TME) has been the premise for improving the effectiveness of AA-based immunotherapy, which hinges upon advanced AA delivery and amplified immune-activating strategies. Herein, a novel Escherichia coli (E. coli) outer membrane vesicle (OMV)-red blood cell (RBC) hybrid membrane (ERm)-camouflaged immunomodulatory nanoturret is meticulously designed based on gating of an AA-immobilized metal-organic framework (MOF) onto bortezomib (BTZ)-loaded magnesium-doped mesoporous silica (MMS) nanovehicles, which can realize immune landscape remodeling by chemotherapy-assisted ascorbate-mediated immunotherapy (CAMIT). Once reaching the acidic TME, the acidity-sensitive MOF gatekeeper and MMS core within the nanoturret undergo stepwise degradation, allowing for tumor-selective sequential release of AA and BTZ. The released BTZ can evoke robust immunogenic cell death (ICD), synergistically promote dendritic cell (DC) maturation in combination with OMV, and ultimately increase T cell tumor infiltration together with Mg2+. The army of T cells is further activated by AA, exhibiting remarkable antitumor and antimetastasis performance. Moreover, the CD8-deficient mice model discloses the T cell-dependent immune mechanism of the AA-based CAMIT strategy. In addition to providing a multifunctional biomimetic hybrid nanovehicle, this study is also anticipated to establish a new immunomodulatory fortification strategy based on the multicomponent-driven nanoturret for highly efficient T cell-activation-enhanced synergistic AA immunotherapy.