Sequence‐Responsive Multifunctional Supramolecular Nanomicelles Act on the Regression of TNBC and Its Lung Metastasis via Synergic Pyroptosis‐Mediated Immune Activation

Abstract 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 O 2 catalyzed by PolyMN‐TO‐8 under laser is indispensable for tumor metastasis inhibition undoubtedly.