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Evoking Ferroptosis by Synergistic Enhancement of a Cyclopentadienyl Iridium‐Betulin Immune Agonist.
- Source :
-
Angewandte Chemie International Edition . 11/27/2023, Vol. 62 Issue 48, p1-12. 12p. - Publication Year :
- 2023
-
Abstract
- Ferroptosis is a form of programmed cell death driven by iron‐dependent lipid peroxidation (LPO) with the potential for antitumor immunity activation. In this study, a nonferrous cyclopentadienyl metal‐based ferroptosis inducer [Ir(Cp*)(Bet)Cl]Cl (Ir‐Bet) was developed by a metal‐ligand synergistic enhancement (MLSE) strategy involving the reaction of [Ir(Cp*)Cl]2Cl2 with the natural product Betulin. The fusion of Betulin with iridium cyclopentadienyl (Ir‐Cp*) species as Ir‐Bet not only tremendously enhanced the antiproliferative activity toward cancer cells, but also activated ferritinophagy for iron homeostasis regulation by PI3K/Akt/mTOR cascade inhibition with a lower dosage of Betulin, and then evoked an immune response by nuclear factor kappa‐B (NF‐κB) activation of Ir‐Cp* species. Further immunogenic cell death (ICD) occurred by remarkable ferroptosis through glutathione (GSH) depletion, glutathione peroxidase 4 (GPX4) deactivation and ferritinophagy. An in vivo vaccination experiment demonstrated desirable antitumor and immunogenic effects of Ir‐Bet by increasing the ratio of cytotoxic T cells (CTLs)/regulatory T cells (Tregs). [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14337851
- Volume :
- 62
- Issue :
- 48
- Database :
- Academic Search Index
- Journal :
- Angewandte Chemie International Edition
- Publication Type :
- Academic Journal
- Accession number :
- 173760440
- Full Text :
- https://doi.org/10.1002/anie.202312897