设计有效的纳米药物来调节肿瘤微环境的免疫抑制是增强临床肿瘤治疗效果的一种可取方法。通过疏水力将超分子主体MTX-MPEG2000、客体NPX-2S和TO-8自组装构建的超分子纳米胶束PolyMN-TO-8具有卓越的稳定性，并对羧酯酶和谷胱甘肽具有响应能力。体内研究验证了PolyMN-TO-8在激光下能够触发促炎症细胞凋亡介导的免疫原性细胞死亡，同时避免了免疫失调的发生。这种治疗方式通过适度激活促炎症因子、加强树突状细胞成熟和促进CD8+T细胞的浸润进而消除免疫逃逸，最终通过光动力治疗、光热疗法、化学疗法等协同作用将肿瘤抑制率提高至87.44%。免疫逃逸的减少加速了CD8+T细胞的浸润进入肺部，进一步避免了肿瘤结节的生成。化学疗法、干扰素-γ的释放和免疫记忆效应也增强了对转移的防御。激光诱导的PolyMN-TO-8产生的O2对于抑制肿瘤转移不可或缺。© 2023 Wiley-VCH GmbH.

Design of effective nanodrugs to modulate the immunosuppression of tumor microenvironment is a desirable approach to boost the clinical tumor-therapeutic effect. Supramolecular nanomicelles PolyMN-TO-8, which are constructed by self-assembling supramolecular host MTX-MPEG2000, guest NPX-2S, and TO-8 through hydrophobic forces, have excellent stability and responsiveness to carboxylesterase and glutathione in turn. In vivo studies validate that PolyMN-TO-8 enable to trigger pyroptosis-mediated immunogenic cell death under laser, avoiding the occurrence of immune dysregulation simultaneously. This therapeutic mode strengthens dendritic cells' maturation and accelerates the infiltration of CD8+ T cells into tumors through moderate activation of pro-inflammatory factors with elimination of immune-escape, ultimately making the tumor inhibition rate as high as 87.44% via synergistic functions of photodynamic therapy, photothermal therapy, chemotherapy, etc. The loss of immune-escape quickens the infiltration of CD8+ T cells into lungs, and further eschews the generation of tumor nodules in it. Chemotherapy, the release of interferon-γ, and immune memory effect also strengthen the defense against metastasis. The generation of O2 catalyzed by PolyMN-TO-8 under laser is indispensable for tumor metastasis inhibition undoubtedly.© 2023 Wiley-VCH GmbH.