Pyroptosis provides a novel perspective for the design of anti‐tumor strategies. However, when pyroptosis reaches a plateau, its negative role becomes “defense” signaling to evade immune surveillance. Herein, a triblock polymeric micelles TPT@PIO NPs are reported, including a hydrophobic block backbone poly (propylene sulfide) (PPS), a hydrophobic side chain disulfide bond‐bearing indomethacin (MABHD‐IND), a hydrophilic block poly(ethylene glycol) methyl ether methacrylate (OEGMA), and an encapsulated hydrophobic drug topotecan (TPT) through hydrophobic forces, exhibit excellent stability and responsiveness to the oxidation‐reduction microenvironment. This dual treatment mode utilizes TPT to trigger the activation of the pyroptosis process and uses IND to eliminate the immune escape by inhibiting the COX‐2/PGE2 pathway, ultimately making the growth of tumors being inhibited via the synergy of chemotherapy and immunotherapy. Furthermore, the failure of the immunosuppressive network accelerates the infiltration of CD8+ T cells into the lungs and impedes the generation of tumor nodules. The changes in levels of cytokines caused by pyroptosis and the immune memory effect enhance the defense of transfer as well. In general, the ability of TPT@PIO NPs to regulate the Janus‐faced nature of pyroptosis acts as an indispensable role in suppressing tumor proliferation and metastasis.

中文翻译：

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一种多前药纳米球，用于调节 Janus 面的焦亡性质，以发起免疫攻势和防御战，重新点燃癌症免疫循环


Pyroptisis 为抗肿瘤策略的设计提供了新的视角。然而，当细胞焦亡达到平台期时，其消极作用成为逃避免疫监视的“防御”信号。在此，报道了一种TPT@PIO NP 的三嵌段聚合物胶束，包括疏水嵌段主链聚（丙硫醚）（PPS）、疏水侧链二硫键含吲哚美辛 （MABHD-IND）、亲水嵌段聚（乙二醇）甲基醚甲基丙烯酸酯 （OEGMA） 和通过疏水力封装的疏水性药物拓扑替康 （TPT），表现出优异的稳定性和对氧化还原微环境的响应性。这种双重治疗模式利用 TPT 触发细胞焦亡过程的激活，并使用 IND 通过抑制 COX-2/PGE2 通路来消除免疫逃逸，最终通过化疗和免疫治疗的协同作用使肿瘤的生长受到抑制。此外，免疫抑制网络的失败加速了 CD8+ T 细胞浸润到肺部并阻碍了肿瘤结节的产生。由焦亡引起的细胞因子水平的变化和免疫记忆效应也增强了对转移的防御。一般来说，TPT@PIO NPs 调节焦亡的 Janus 面性质的能力在抑制肿瘤增殖和转移中起着不可或缺的作用。