Simultaneous Fenton-like Ion Delivery and Glutathione Depletion by MnO2-Based Nanoagent to Enhance Chemodynamic Therapy

Chemodynamic therapy (CDT) utilizes iron-initiated Fenton chemistry to destroy tumor cells by converting endogenous H2O2 into the highly toxic hydroxyl radical ((OH)-O-.). There is a paucity of Fenton-like metal-based CDT agents. Intracellular glutathione (GSH) with center dot OH scavenging ability greatly reduces CDT efficacy. A self-reinforcing CDT nanoagent based on MnO2 is reported that has both Fenton-like Mn2+ delivery and GSH depletion properties. In the presence of HCO3-, which is abundant in the physiological medium, Mn2+ exerts Fenton-like activity to generate center dot OH from H2O2. Upon uptake of MnO2-coated mesoporous silica nanoparticles (MS@MnO2 NPs) by cancer cells, the MnO2 shell undergoes a redox reaction with GSH to form glutathione disulfide and Mn2+, resulting in GSH depletion-enhanced CDT. This, together with the GSH-activated MRI contrast effect and dissociation of MnO2, allows MS@MnO2 NPs to achieve MRI-monitored chemo-chemodynamic combination therapy.