Biomimetic Nanozyme-Decoys Reprogram Immune Niches to Intercept Colitis-Carcinoma Transition

Colitis-associated colorectal cancer (CAC) arises from chronic inflammatory niches characterized by persistent oxidative stress and dysregulated immune cell recruitment. Current anti-inflammatory therapies provide only transient symptom relief and fail to prevent malignant progression due to their inability to simultaneously mitigate oxidative injury and immune chemotaxis. Our analysis of clinical samples revealed markedly elevated C-X-C motif chemokine ligand 2 (CXCL2) in intestinal tissues from patients with inflammatory bowel disease and CAC, implicating the CXCL2-CXCR2 (C-X-C motif chemokine receptor 2) axis in driving excessive neutrophil and macrophage infiltration and fostering tumorigenesis. Herein, we report a biomimetic nanozyme (PB@ECM) that reprograms inflammatory immune niches to intercept CAC progression. PB@ECM integrates a Prussian blue nanozyme core with genetically engineered macrophage membranes, enabling concurrent scavenging of reactive oxygen species through superoxide dismutase- and catalase-like activities and sequestration of CXCL2 via membrane-displayed CXCR2 receptors. In murine models of colitis and CAC, PB@ECM significantly alleviated intestinal inflammation, suppressed neutrophil and macrophage infiltration, and effectively inhibited colitis-carcinoma transition. Notably, treatment with PB@ECM significantly prolonged survival compared with other groups. By disrupting the pathological crosstalk between oxidative stress and immune chemotaxis, this work establishes a biomimetic nanozyme strategy for preventing inflammation-driven carcinogenesis.