FerriIridium: A Lysosome-Targeting Iron(III)-Activated Iridium(III) Prodrug for Chemotherapy in Gastric Cancer Cells.
Shi KuangXinxing LiaoXianrui ZhangThomas W ReesRuilin GuanKai XiongYu ChenLiangnian JiHui ChaoPublished in: Angewandte Chemie (International ed. in English) (2020)
Reported is the FeIII -activated lysosome-targeting prodrug FerriIridium for gastric cancer theranostics. It contains a meta-imino catechol group that can selectively bond to, and be oxidized by, free FeIII inside the cell. Subsequent oxidative rearrangement releases FeII and hydrolyses the amine bond under acidic conditions, forming an aminobipyridyl Ir complex and 2-hydroxybenzoquinone. Thus, FeII catalyzes the Fenton reaction, transforming hydrogen peroxide into hydroxyl radicals, the benzoquinone compounds interfere with the respiratory chain, and conversion of the prodrug into the Ir complex leads to an increase in phosphorescence and toxicity. These properties, combined with the high FeIII content and acidity of cancer cells, make FerriIridium a selective and efficient theranostic agent (IC50 =9.22 μm for AGS cells vs. >200 μm for LO2 cells). FerriIridium is the first metal-based compound that has been developed for chemotherapy using FeIII to enhance both selectivity and potency.
Keyphrases
- hydrogen peroxide
- cancer therapy
- induced apoptosis
- cell cycle arrest
- nitric oxide
- drug delivery
- oxidative stress
- drug release
- locally advanced
- endoplasmic reticulum stress
- stem cells
- single cell
- fluorescent probe
- room temperature
- signaling pathway
- cell death
- photodynamic therapy
- ionic liquid
- fluorescence imaging
- cell therapy