Advances in iron-based chemodynamic anti-cancer therapy

Iron-based chemodynamic therapy (CDT) is an emerging cancer treatment strategy that utilizes the overexpression of hydrogen peroxide (H₂O₂) and mild acidity within the tumor microenvironment. This approach generates highly toxic hydroxyl radicals (·OH) within tumors through iron-ion-catalyzed Fenton or Fenton-like reactions, enabling selective tumor cell ablation while minimizing damage to healthy tissues. Iron is recognized as an ideal catalytic metal for CDT due to its excellent biocompatibility, tumor-targeting potential, and versatile theragnostic capabilities. This review explains the core mechanisms of iron-based CDT, analyzes the inherent limitations posed by the tumor microenvironments, and comprehensively summarizes advanced iron-based nanomaterials designed to overcome these challenges, including inorganic nano catalysts, organic-inorganic hybrids, and biomimetic nanostructures. Furthermore, it highlights multidimensional strategies to enhance CDT efficacy: actively remodeling the tumor microenvironment by modulating H₂O₂ supply, pH, antioxidant defenses and hypoxia; using external stimuli such as light, ultrasound, or magnetic fields to remotely activate and amplify reactions; and achieving synergistic effects by combining with chemotherapy, radiotherapy, and immunotherapy. Finally, the review outlines key challenges in the clinical translation of iron-based CDT and suggests future research directions, providing a comprehensive and timely perspective on this rapidly advancing field.