Chimeric Nanozyme Bacterial Outer Membrane Vesicles Reprograming Tumor Microenvironment for Safe and Efficient Anticancer Therapy

Abstract This study presents an innovative approach utilizing a biocompatible shell to shield bacterial outer membrane vesicles (OMVs) and incorporate Fe ions and ultrasmall Au nanoparticles to develop a combined tumor therapeutic strategy. These chimeric nanozyme shells effectively reduce the toxicity of OMVs during circulation and promote their accumulation in tumor tissues. In the tumor microenvironment, Au nanoparticles act as nanozymes, catalyzing glucose consumption and elevating H₂O₂ levels. The increased H₂O₂ subsequently reacts with the released Fe ions to induce immunogenic tumor cell death through iron‐mediated chemodynamic mechanisms. Simultaneously, the release of tumor‐associated antigens and OMVs synergistically stimulates the immune response. This cascade of nanozyme‐catalyzed reactions, chemodynamic effects, and immune activation results in efficient tumor inhibition.