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Gong, Fei; Chen, Muchao; Yang, Nailin; Dong, Ziliang; Tian, Longlong; Hao, Yu; Zhuo, Mingpeng; Liu, Zhuang; Chen, Qian; Cheng, Liang
Advanced functional materials, December 1, 2020, Letnik: 30, Številka: 49Journal Article
Modulating the hostile tumor microenvironment (TME) rather than directly killing cancer cells may be an effective strategy to improve the therapeutic benefits in cancer treatment. Herein, FeWOX nanosheets are constructed as cascade bioreactors to modulate the TME and enhance radiotherapy and immunotherapy of tumors. Synthesized by the thermal‐decomposition method and modified by poly(ethylene glycol) (PEG), the obtained FeWOX‐PEG with multivalent metal elements (Fe2+/3+, W5+/6+) exhibit efficient catalytic decomposition of hydrogen peroxide (H2O2) to generate hydroxyl radicals (•OH) for chemo‐dynamic therapy (CDT). The generated high valence of metal ions (Fe3+/W6+) in FeWOX‐PEG are reduced by endogenous glutathione (GSH), both leading to depletion of GSH and further amplified oxidative stress, and resulting in the reduced metal valence statuses (Fe2+/W5+) enabling cascade bioreactions. Such FeWOX‐PEG bioreactors enhance the oxidative stress in the tumor and interact with X‐rays, significantly improving cancer radiotherapy (RT). Furthermore, the reactive oxygen species (ROS)‐induced inflammation caused by FeWOX‐PEG in TME activates the immune system and promotes the tumor‐infiltration of various types of immune cells, which working together with cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) checkpoint blockade could elicits a robust immune response to defeat tumors. This work presents an intelligent cascade bioreactor based on multivalent bimetallic oxide FeWOX nanosheets, which exhibit efficient catalytic decomposition of hydrogen peroxide (H2O2) to generate hydroxyl radicals (•OH), as well as glutathione depletion capability to further amplify oxidative stress. This good tumor microenvironment‐modulation performance can further enhance both radiotherapy and immunotherapy of tumors.
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