Persistent glutathione-depleting MFO@MIL nanoreactors enhance antitumor efficiency of 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 the iron-based metal organic frameworks (MIL-101). The MFO@MIL is then incorporated into polycaprolactone (PCL) to prepare a porous skin scaffold, aiming to continuously release of MFO@MIL and simultaneously regulate intracellular reducibility and ROS yield to enhance anti-tumor efficacy. Particularly, the MnFe2O4 with GSH peroxidase-like ability can persistently deplete GSH to decrease the consumption of hydroxyl radical (•OH) generated by Fenton reaction between MIL-101 with hydrogen peroxide (H2O2). Meanwhile, the depletion process of MnFe2O4 will produce Mn2+, which collaborates with the MIL-101 to continuously catalyze H2O2 to produce •OH, remarkably increasing •OH yield and enhancing anti-tumor efficacy. Results showed that the depletion rate of GSH by the scaffold reached 84.4% within 24 hours. The •OH yield of the scaffold is 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 versatile strategy to significantly enhance ROS-based anti-tumor efficacy and potentially extend it to multiple tumors.