期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 59, 期 50, 页码 22537-22543出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202003653
关键词
antitumor agents; cofactors; DNA; nanostructures; zeolites
资金
- National Funds for Distinguished Young Scientists [51725202]
- Key Project of Shanghai Science and Technology Commission [19JC1412000]
- National Natural Science Foundation of China [51872094]
- National Science Foundation for the Young Scientists of China [51702211, 21805090]
- National Key R&D Program of China [2018YFA0107900]
- Collaborative Innovation Center of Technology and Equipment for Biological Diagnosis and Therapy in Universities of Shandong
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.
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