From Rational Design to Druggability Optimization: A Review of Iron-based Nanozymes for Biomedical Applications

Iron-based nanozymes mimic key enzymatic activities while offering the design flexibility and stability of nanomaterials. Advances in single-atom engineering, defect modulation, biomimetic synthesis, and multienzyme synergy have expanded their peroxidase (POD)-, catalase (CAT)-, superoxide dismutase (SOD)-, and oxidase (OXD)-like functions, enabling broad biomedical applications in cancer therapy, infection control, neuroprotection, and diagnostics. However, key druggability challenges, such as synthesis reproducibility, structural and functional stability, controllable pharmacokinetics, and immunological safety, continue to hinder clinical translation. This Review provides a comprehensive and structured analysis of iron-based nanozymes from the perspective of druggability optimization. It highlights recent progress in catalytic mechanism elucidation, structure–activity relationship engineering, responsive behavior tuning, and therapeutic performance evaluation. The emphasis is placed on the integration of artificial intelligence (AI) for rational design, the development of standardized characterization and quality control protocols, and the implementation of scalable, good manufacturing practice (GMP)-compliant production pathways. By aligning catalytic innovation with translational requirements, iron-based nanozymes are advancing toward next-generation theranostic platforms capable of microenvironmental remodeling and intelligent treatment integration.