BQ-AurIPr: A Redox-Active Anticancer Au(I) Complex that Induces Immunogenic Cell Death in Non-Small Cell Lung Cancer

18 March 2022, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Immunogenic Cell Death (ICD) is a unique cell death mechanism that kills cancer cells while rejuvenating the anti-cancer immunosurveillance, thereby benefiting the clinical outcomes of various chemo-immunotherapeutic 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 in-duce 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 ICD induction.

Keywords

Immunogenic Cell Death
Gold Complexes
Anticancer Activity
Mitophagy
Phagocytosis

Supplementary materials

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Title
BQ-AurIPr: A Redox-Active Anticancer Au(I) Complex that Induces Immunogenic Cell Death in Non-Small Cell Lung Cancer
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