Persistent glutathione-depleting MFO@MIL nanoreactors enhance the antitumor efficiency of a skin scaffold†

The efficacy of reactive oxygen species (ROS)-related skin tumor therapies is significantly restricted by intracellular overexpressed glutathione (GSH) which is a free radical scavenger. Herein, a GSH-depleting and high ROS production nanoreactor (MFO@MIL) is constructed by in situ loading manganese ferrite (MnFe₂O₄) onto an iron-based metal organic framework (MIL-101). The MFO@MIL is then incorporated into polycaprolactone (PCL) to prepare a porous skin scaffold, aiming to continuously release MFO@MIL and simultaneously regulate intracellular reducibility and ROS yield to enhance anti-tumor efficacy. Particularly, MnFe₂O₄ with GSH peroxidase-like activity can persistently deplete GSH to reduce its consumption of hydroxyl radicals (˙OH), which are produced by the Fenton reaction between MIL-101 and hydrogen peroxide (H₂O₂). Meanwhile, the depletion process of MnFe₂O₄ to GSH will produce Mn²⁺, which collaborates with MIL-101 to catalyze H₂O₂ to produce ˙OH, remarkably increasing ˙OH yield and enhancing anti-tumor efficacy. The results showed that the depletion rate of GSH using the scaffold reached 84.4% within 24 hours. The ˙OH yield of the scaffold was significantly higher than that of the scaffold loaded with MIL-101 alone. Systematic cell experiments demonstrated the powerful anti-tumor efficacy of the scaffold. This study proposes a feasible strategy to enhance ROS-based anti-tumor efficacy.