Cascaded Nanozyme with In Situ Enhanced Photothermal Capacity for Tumor‐Specific and Self‐Replenishing Cancer Therapy

Abstract Reactive oxygen species (ROS)‐involved tumor therapeutic strategy, chemodynamic therapy (CDT), has attracted extensive research interest in the scientific community. However, the therapeutic effect of CDT is insufficient and unsustainable owing to the limited endogenous H2O2 level in the tumor microenvironment. Here, peroxidase (POD)‐like RuTe2 nanozyme with the immobilization of glucose oxidase (GOx) and allochroic 3,3′,5,5′‐tetramethylbenzidine (TMB) molecule have been synthesized to construct RuTe2‐GOx‐TMB nanoreactors (RGT NRs) as cascade reaction systems for tumor‐specific and self‐replenishing cancer therapy. GOx in sequential nanocatalysts can effectively deplete glucose in tumor cells. Meanwhile, a sustainable supply of H2O2 for subsequent Fenton‐like reactions catalyzed by RuTe2 nanozyme is achieved in response to the mild acidic tumor microenvironment. Through this cascade reaction, highly toxic hydroxyl radicals (·OH) are produced, which can further oxidize TMB to trigger tumor‐specific “turn‐on” photothermal therapy (PTT). In addition, PTT and massive ROS can stimulate the tumor immune microenvironment and activate the systematic anti‐tumor immune responses, exerting a notable effect on hindering tumor recurrence and metastasis. This study paves a promising paradigm for synergistic starvation therapy, PTT, and CDT cancer therapy with high efficiency.