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Redox Dyshomeostasis Strategy for Hypoxic Tumor Therapy Based on DNAzyme‐Loaded Electrophilic ZIFs
Author(s) -
Li Yanli,
Zhao Peiran,
Gong Teng,
Wang Han,
Jiang Xingwu,
Cheng Hui,
Liu Yanyan,
Wu Yelin,
Bu Wenbo
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202003653
Subject(s) - reactive oxygen species , chemistry , redox , glutathione , electrophile , tumor hypoxia , intracellular , hypoxia (environmental) , in vivo , biophysics , biochemistry , microbiology and biotechnology , cancer research , oxygen , catalysis , biology , medicine , enzyme , organic chemistry , radiation therapy
Redox homeostasis is one of the main reasons for reactive oxygen species (ROS) tolerance in hypoxic tumors, limiting ROS‐mediated tumor therapy. Proposed herein is a redox dyshomeostasis (RDH) strategy based on a nanoplatform, FeCysPW@ZIF‐82@CAT Dz, to disrupt redox homeostasis, and its application to improve ROS‐mediated hypoxic tumor therapy. Once endocytosed by tumor cells, the catalase DNAzyme (CAT Dz) loaded zeolitic imidazole framework‐82 (ZIF‐82@CAT Dz) shell can be degraded into Zn 2+ as cofactors for CAT Dz mediated CAT silencing and electrophilic ligands for glutathione (GSH) depletion under hypoxia, both of which lead to intracellular RDH and H 2 O 2 accumulation. These “disordered” cells show reduced resistance to ROS and are effectively killed by ferrous cysteine‐phosphotungstate (FeCysPW) induced chemodynamic therapy (CDT). In vitro and in vivo data demonstrate that the pH/hypoxia/H 2 O 2 triple stimuli responsive nanocomposite can efficiently kill hypoxic tumors. Overall, the RDH strategy provides a new way of thinking about ROS‐mediated treatment of hypoxic tumors.