A Ferrocene-Functionalized Covalent Organic Framework for Enhancing Chemodynamic Therapy via Redox Dyshomeostasis.
Le-Le ZhouQun GuanWen-Yan LiZhiyong ZhangYan-An LiYu-Bin DongPublished in: Small (Weinheim an der Bergstrasse, Germany) (2021)
Chemodynamic therapy (CDT), which induces cell death by decomposing high levels of H2 O2 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.
Keyphrases
- oxidative stress
- cell death
- induced apoptosis
- reactive oxygen species
- diabetic rats
- cell cycle arrest
- hydrogen peroxide
- ischemia reperfusion injury
- cancer therapy
- drug delivery
- dna damage
- cell therapy
- single cell
- water soluble
- wastewater treatment
- high glucose
- endoplasmic reticulum stress
- cell proliferation
- electron transfer
- high resolution
- mass spectrometry
- drug induced
- heat shock
- heat shock protein