Specific Generation of Singlet Oxygen through the Russell Mechanism in Hypoxic Tumors and GSH Depletion by Cu‐TCPP Nanosheets for Cancer Therapy
Abstract
The generation of singlet oxygen (1 O 2) during photodynamic therapy is limited by the precise cooperation of light, photosensitizer, and oxygen, and the therapeutic efficiency is restricted by the elevated glutathione (GSH) levels in cancer cells. Herein, we report that an ultrathin two‐dimensional metal–organic framework of Cu‐TCPP nanosheets (TCPP=tetrakis(4‐carboxyphenyl)porphyrin) can selectively generate 1 O 2 in a tumor microenvironment. This process is based on the peroxidation of the TCPP ligand by acidic H 2 O 2 followed by reduction to peroxyl radicals under the action of the peroxidase‐like nanosheets and Cu 2+, and their spontaneous recombination reaction by the Russell mechanism. In addition, the nanosheets can also deplete GSH. Consequently, the Cu‐TCPP nanosheets can selectively destroy tumor cells with high efficiency, constituting an attractive way to overcome current limitations of photodynamic therapy.
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Nanoparticles can generate superoxide radicals while splitting water to produce oxygen, which can promote photodynamic therapy against tumors.
“Recently, several studies have shown that nanoparticles can also generate superoxide radicals while splitting water to produce oxygen, which can promote photodynamic therapy against tumors. 443 , 444 , 445 , 446”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [444]
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- Authors
- Wang, C., Cao, F., Ruan, Y., Jia, X., Zhen, W., & Jiang, X.
- Affiliations
- University of Science and Technology of China (CN)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Jiang, Xiue
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2019-06-07
- Volume
- 58
- Issue
- 29
- Pages
- 9846-9850
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- OpenAlex
- W2948231961
- Cited by
- 411
- References
- 39
- Citations by year
- 2026: 23 · 2025: 48 · 2024: 53 · 2023: 52 · 2022: 68 · 2021: 101 · 2020: 56 · 2019: 10
- FWCI
- 20.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Angewandte Chemie International Edition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (21675149, 21705146, 21874125)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Physical Sciences › Materials Science › Materials Chemistry › Porphyrin and Phthalocyanine Chemistry
- Keywords
- singlet oxygen generation, photodynamic therapy, hypoxic tumors, glutathione depletion, tetrakis(4-carboxyphenyl)porphyrin, metal-organic framework nanosheets, peroxy radicals, peroxidase-like activity, tumor microenvironment, nanosheets, cancer therapy
- MeSH terms
- Glutathione, Humans, Neoplasms, Oxygen, Photochemotherapy, Cell Hypoxia, Singlet Oxygen, Nanostructures, Tumor Microenvironment
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