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

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 O₂ 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.