Issue 36, 2022

BQ-AurIPr: a redox-active anticancer Au(i) complex that induces immunogenic cell death

Abstract

Immunogenic Cell Death (ICD) is a unique cell death mechanism that kills cancer cells while rejuvenating the anticancer immunosurveillance, thereby benefiting the clinical outcomes of various immuno-chemotherapeutic regimens. Herein, we report development of a library of benzo[a]quinolizinium-based Au(I) complexes through an intramolecular amino-auration reaction of pyridino-alkynes. We tested 40 candidates and successfully identified BQ-AurIPr as a novel redox-active Au(I) complex with potent anticancer properties. BQ-AurIPr efficiently triggered generation of DAMPs – the hallmarks of ICD – and was superior in terms of efficiency compared to FDA-approved drugs known to induce ICD. BQ-AurIPr significantly increased immunogenicity of cancer cells enhancing their phagocytosis when co-cultured with immune cells. Our investigation reveals that BQ-AurIPr induces oxidative stress inside mitochondria leading to mitophagy, as the mechanism for immunogenic cell death in A549 cells.

Graphical abstract: BQ-AurIPr: a redox-active anticancer Au(i) complex that induces immunogenic cell death

Supplementary files

Article information

Article type
Edge Article
Submitted
06 jul 2022
Accepted
24 aug 2022
First published
25 aug 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2022,13, 10779-10785

BQ-AurIPr: a redox-active anticancer Au(I) complex that induces immunogenic cell death

R. D. Mule, A. Kumar, S. P. Sancheti, B. Senthilkumar, H. Kumar and N. T. Patil, Chem. Sci., 2022, 13, 10779 DOI: 10.1039/D2SC03756D

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