Amorphous Ultra‐Small Fe‐Based Nanocluster Engineered and ICG Loaded Organo‐Mesoporous Silica for GSH Depletion and Photothermal‐Chemodynamic Synergistic Therapy

Abstract Intracellular oxidative amplification can effectively destroy tumor cells. Additionally, Fe‐mediated Fenton reaction often converts cytoplasm H 2 O 2 to generate extensive hypertoxic hydroxyl radical ( • OH), leading to irreversible mitochondrion damage for tumor celleradication, which is widely famous as tumor chemodynamic therapy (CDT). Unfortunately, intracellular overexpressed glutathione (GSH) always efficiently scavenges • OH, resulting in the significantly reduced CDT effect. To overcome this shortcoming and improve the oxidative stress in cytoplasm, Fe 3 O 4 ultrasmall nanoparticle encapsulated and ICG loaded organo‐mesoporous silica nanovehicles (omSN@Fe‐ICG) are constructed to perform both photothermal and GSH depletion to enhance the Fenton‐like CDT, by realizing intracellular oxidative stress amplification. After this nanoagents are internalized, the tetrasulfide bonds in the dendritic mesoporous framework can be decomposed with GSH to amplify the toxic ROS neration by selectively converting H 2 O 2 to hydroxyl radicals through the released Fe‐based nanogranules. Furthermore, the NIR laser‐induced hyperthermia can further improve the Fenton reaction rate that simultaneously destroyed the mitochondria. As a result, the GSH depletion and photothermal assisted CDT can remarkably improve the tumor eradication efficacy.