PUBLICATION
Cyclometalated Gold(III)-Hydride Complexes Exhibit Visible Light-Induced Thiol Reactivity and Act as Potent Photo-Activated Anti-Cancer Agents
- Authors
- Luo, H., Cao, B., Chan, A.S.C., Sun, R.W., Zou, T.
- ID
- ZDB-PUB-200403-170
- Date
- 2020
- Source
- Angewandte Chemie (International ed. in English) 59(27): 11046-11052 (Journal)
- Registered Authors
- Keywords
- Thioredoxin reductase, anti-cancer, gold medicine, photoactivatable prodrug, thiol reactivity
- MeSH Terms
-
- Animals
- Antineoplastic Agents/chemistry*
- Cell Line, Tumor
- Gold/chemistry*
- Light*
- Proton Magnetic Resonance Spectroscopy
- Spectrometry, Mass, Electrospray Ionization
- Sulfhydryl Compounds/chemistry*
- Zebrafish/embryology
- PubMed
- 32207866 Full text @ Angew. Chem. Int. Ed. Engl.
Citation
Luo, H., Cao, B., Chan, A.S.C., Sun, R.W., Zou, T. (2020) Cyclometalated Gold(III)-Hydride Complexes Exhibit Visible Light-Induced Thiol Reactivity and Act as Potent Photo-Activated Anti-Cancer Agents. Angewandte Chemie (International ed. in English). 59(27):11046-11052.
Abstract
The specific gold-sulfur binding interaction renders gold complexes to be promising anti-cancer agents that can potentially overcome cisplatin resistance; while their unbiased binding towards non-tumoral off-target thiol-proteins has posed a big hurdle to clinical application. Herein we report that cyclometalated gold(III) complexes bearing hydride ligands are highly stable towards thiols in the dark but can efficiently dissociate the auxiliary hydride moiety and generate gold-thiol adduct when excited with visible light. In consequence, the photo-activated gold(III) complexes potently inhibited thioredoxin reductase in association with up to >400-fold increment of photocytotoxicity (vs dark condition) without deactivation by serum albumin and along with strong anti-angiogenesis activity in zebrafish embryos. Importantly, the gold(III)-hydride complexes could be activated by two-photon laser irradiation at the phototherapeutic window as effectively as blue light irradiation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping