Glutathione Depletion in a Benign Manner by MoS 2 -Based Nanoflowers for Enhanced Hypoxia-Irrelevant Free-Radical-Based Cancer Therapy

Tumor hypoxia significantly diminishes the efficacy of reactive oxygen species (ROS)-based therapy, mainly because the generation of ROS is highly oxygen dependent. Recently reported hypoxia-irrelevant radical initiators (AIBIs) exhibit promising potential for cancer therapy under different oxygen tensions. However, overexpressed glutathione (GSH) in cancer cells would potently scavenge the free radicals produced from AIBI before their arrival to the specific site and dramatically limit the therapeutic efficacy. A synergistic antitumor platform (MoS @AIBI-PCM nanoflowers) is constructed by incorporating polyethylene-glycol-functionalized molybdenum disulfide (PEG-MoS ) nanoflowers with azo initiator and phase-change material (PCM). Under near-infrared laser (NIR) irradiation, the photothermal feature of PEG-MoS induces the decomposition of AIBI to produce free radicals. Furthermore, PEG-MoS can facilitate GSH oxidation without releasing toxic metal ions, greatly promoting tumor apoptosis and avoiding the introduction of toxic metal ions. This is the first example of the use of intelligent MoS -based nanoflowers as a benign GSH scavenger for enhanced cancer treatment.