A Ferrocene‐Functionalized Covalent Organic Framework for Enhancing Chemodynamic Therapy via Redox Dyshomeostasis

Chemodynamic therapy (CDT), which induces cell death by decomposing high levels of H2O2 in tumor cells into highly toxic ·OH, is recognized as a promising antineoplastic approach. However, current CDT approaches are often restricted by the highly controlled and upregulated cellular antioxidant defen...

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Vydáno v:Small (Weinheim an der Bergstrasse, Germany) Ročník 17; číslo 32; s. e2101368 - n/a
Hlavní autoři: Zhou, Le‐Le, Guan, Qun, Li, Wen‐Yan, Zhang, Zhiyong, Li, Yan‐An, Dong, Yu‐Bin
Médium: Journal Article
Jazyk:angličtina
Vydáno: Weinheim Wiley Subscription Services, Inc 01.08.2021
Témata:
Antioxidants
cancer
Cell death
chemodynamic therapy
Covalence
covalent organic frameworks
Damage accumulation
ferroptosis
Glutathione
Hydrogen peroxide
Lipids
nanoparticles
Nanotechnology
Peroxidase
ISSN:1613-6810, 1613-6829, 1613-6829
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Shrnutí:Chemodynamic therapy (CDT), which induces cell death by decomposing high levels of H2O2 in tumor cells into highly toxic ·OH, is recognized as a promising antineoplastic approach. However, current CDT approaches are often restricted by the highly controlled and upregulated cellular antioxidant defense. To enhance ·OH‐induced cellular damage by CDT, a covalent organic framework (COF)‐based, ferrocene (Fc)‐ and glutathione peroxidase 4 (GPX4) inhibitor‐loaded nanodrug, RSL3@COF–Fc (2b), is fabricated. The obtained 2b not only promotes in situ Fenton‐like reactions to trigger ·OH production in cells, but also attenuates the repair mechanisms under oxidative stress via irreversible covalent GPX4 inhibition. As a result, these two approaches synergistically result in massive lipid peroxide accumulation, subsequent cell damage, and ultimately ferroptosis, while not being limited by intracellular glutathione. It is believed that this research provides a paradigm for enhancing reactive oxygen species‐mediated oncotherapy through redox dyshomeostasis and may provide new insights for developing COF‐based nanomedicine. Versatile covalent organic frameworks (COFs)! The organic nanodrug RSL3@COF–Fc (2b), which integrates the glutathione peroxidase 4 inhibitor RSL3 and Fenton‐like reaction catalyst ferrocene (Fc) into a nanoscale COF, induces ferroptosis to enhance chemodynamic therapy by blocking lipid repair and disrupting cellular redox homeostasis.
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ISSN:1613-6810
1613-6829
1613-6829
DOI:10.1002/smll.202101368