Engineered Nanozymes for Colorectal Cancer Therapy: Catalytic Reprogramming of the Tumor Microenvironment

Colorectal cancer (CRC) remains difficult to treat because redox adaptation, metabolic plasticity, mucin-associated delivery barriers, immune exclusion, and microbiota-dependent signaling jointly limit conventional therapy. Engineered nanozymes provide a reaction-centered strategy for exploiting these CRC-specific vulnerabilities. This review critically compares metal, metal-oxide, carbon-based, porous-framework, and single-atom nanozymes with respect to catalytic mechanism, enzyme-mimicking activity, substrate dependence, controllability, biosafety, and translational suitability. We examine how acidity, hydrogen peroxide, hypoxia, glutathione enrichment, metabolic dysregulation, mucin barriers, and the gut microbiota influence catalytic performance. We further evaluate evidence for chemotherapy sensitization, chemodynamic, photothermal, photodynamic, sonodynamic, immunotherapeutic, and multimodal treatment, emphasizing both mechanistic synergy and limitations of the available preclinical models. Major translational barriers include non-standardized catalytic assays, heterogeneous intratumoral substrates, off-target reactive oxygen species toxicity, uncertain degradation and long-term fate, microbiome disruption, manufacturing reproducibility, and limited validation in orthotopic, immunocompetent, organoid, and patient-derived systems. We therefore position CRC nanozyme therapy as a disease-oriented catalytic medicine platform whose clinical value will depend on biomarker-guided selection, programmable activation, and degradable, locally controllable designs.