A Powerful Tumor Catalytic Therapy by an Enzyme‐Nanozyme Cascade Catalysis (ENCAT) System

Abstract Complexity of tumor and its microenvironment as obstacles often restrict traditional tumor therapies. Enzyme/nanozyme‐mediated catalytic therapy has been emerged, but the efficacy of single catalytic therapy is still moderate. Inspired by the concepts of catalytic and synergetic therapy, an enzyme‐nanozyme cascade catalysis (ENCAT)‐enhanced tumor therapy is developed. First, metal–organic framework (MOF) PCN222‐Mn (PM) and glucose oxidase (GOx) are chosen as nanozyme and natural enzyme, respectively. Then two assembled together to form enzyme‐nanozyme complex PCN222‐Mn@GOx (PMG). To achieve tumor targeting and GOx protection, hyaluronic acid (HA) is modified on PMG to obtain PCN222‐Mn@GOx/HA (PMGH). Both cellular and animal studies demonstrate a cascade catalysis‐enhanced tumor therapy by PMGH. Specifically, a cascade catalysis‐enhanced PDT is achieved based on enzyme‐nanozyme mediated cascade‐catalyzed O 2 generation; an enhanced synergistic therapy is demonstrated by combining PM‐mediated PDT, GOx‐mediated starvation therapy, and activated/promoted immunotherapy together. Additionally, the designed tumor catalytic therapy is explored in a tumor bearing mouse model, where it exhibits powerful anti‐tumor effects against both primary and metastatic tumors. This strategy has the potential to broaden tumor therapeutic approaches.