Heterojunction-driven MXenzyme biocatalysis: a progressive strategy to remodel tumor immune microenvironments for improved therapeutic efficacy

The hypoxic and immunosuppressive tumor microenvironment (TME) significantly impedes reactive oxygen species (ROS) generation and suppresses the release of tumor-associated antigens, thereby limiting the induction of immunogenic cell death (ICD) and compromising therapeutic outcomes. Reprogramming this immunosuppressive TME is therefore crucial for effective cancer treatment. In this study, we developed a heterojunction-engineered MXenzyme-based platform (NbMR@EDM) to address this challenge. By leveraging the exceptional photothermal conversion capability and multi-enzymatic activities of Nb₂C MXene, and further enhancing its physiological stability and catalytic performance through <i>in situ</i> loading of MnO_<i>x</i> and metal-polyphenol encapsulation, we constructed a robust nanoplatform for synergistic photothermal/enzymatic/immunotherapy. This system effectively catalyzes the generation of a cytotoxic ROS storm within tumor cells, while its catalase-like activity alleviates tumor hypoxia and augments type-II photodynamic therapy. Subsequently, the induced ICD, together with the released TLR7/8 agonist R848, promotes dendritic cell maturation and enhances T-cell infiltration, ultimately reversing the immunosuppressive TME. This work provides a promising strategy for TME reprogramming and demonstrates significant antitumor efficacy in triple-negative breast cancer, highlighting its broad potential in advancing cancer immunotherapy.