The tumor microenvironment (TME) presents coupled barriers, including hypoxia, acidity, elevated hydrogen peroxide levels, and high glutathione levels, which limit the efficacy of conventional cancer therapies. Hemin, an iron protoporphyrin cofactor of hemoglobin, has emerged as a versatile catalytic node for engineered nanozymes, enabling programmable redox modulation within the TME. Through rational nanoengineering, hemin-based architectures integrate chemodynamic, photodynamic, ferroptotic, and metabolic pathways to amplify reactive oxygen species, recycle oxygen, deplete antioxidant defense, and induce iron-dependent cell death. This Review examines the developments in hemin nanotechnology, with an emphasis on precision assembly, material engineering, cascade nanoreactors, and biological modulation. We have distilled these developments into a rational design toolbox that guides scaffold selection, coordination tuning, spatial programming, and translational optimization, establishing principles for next-generation tumor-adaptive redox nanomaterials.
Alsharabasy et al. (Wed,) studied this question.