PUBLICATION
Alkylgold(III) Complexes Undergo Unprecedented Photo-Induced β-Hydride Elimination and Reduction for Targeted Cancer Therapy
- Authors
- Jiang, J., Cao, B., Chen, Y., Luo, H., Xue, J., Xiong, X., Zou, T.
- ID
- ZDB-PUB-220301-1
- Date
- 2022
- Source
- Angewandte Chemie (International ed. in English) 61(16): e202201103 (Journal)
- Registered Authors
- Keywords
- Anti-Cancer Metallodrug, Gold Medicine, Metal Prodrug, Photoactivated Chemotherapy, Thioredoxin Reductase
- MeSH Terms
-
- Antineoplastic Agents*/pharmacology
- Antineoplastic Agents*/therapeutic use
- Cell Line, Tumor
- Coordination Complexes*/pharmacology
- Coordination Complexes*/therapeutic use
- Gold
- Humans
- Ligands
- Neoplasms*/drug therapy
- Neoplasms*/pathology
- Thioredoxin-Disulfide Reductase
- PubMed
- 35165986 Full text @ Angew. Chem. Int. Ed. Engl.
Citation
Jiang, J., Cao, B., Chen, Y., Luo, H., Xue, J., Xiong, X., Zou, T. (2022) Alkylgold(III) Complexes Undergo Unprecedented Photo-Induced β-Hydride Elimination and Reduction for Targeted Cancer Therapy. Angewandte Chemie (International ed. in English). 61(16):e202201103.
Abstract
Spatiotemporally controllable activation of prodrugs within tumors is highly desirable for cancer therapy to minimize toxic side effects. Herein we report that stable alkylgold(III) complexes can undergo unprecedented photo-induced β-hydride elimination, releasing alkyl ligands and forming gold(III)-hydride intermediates that could be quickly converted into bioactive [AuIII -S] adducts; meanwhile, the remaining alkylgold(III) complexes can photo-catalytically reduce [AuIII -S] into more bioactive AuI species. Such photo-reactivities make it possible to functionalize gold complexes on the auxiliary alkyl ligands without attenuating the metal-biomacromolecule interactions. As a result, the gold(III) complexes containing glucose-functionalized alkyl ligands displayed efficient and tumor-selective uptake; notably, after one- or two-photon activation, the complexes exhibited high thioredoxin reductase (TrxR) inhibition, potent cytotoxicity, and strong antiangiogenesis and antitumor activities in vivo.
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
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