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

Area of Science:

• Medicinal Chemistry
• Immunology
• Cancer Biology

Background:

• Immunogenic Cell Death (ICD) is a crucial mechanism for cancer cell elimination and immune system activation.
• Existing ICD-inducing chemotherapeutics offer benefits but have limitations.
• Novel therapeutic strategies are needed to enhance anti-cancer immunosurveillance.

Purpose of the Study:

• To develop novel gold(I) complexes capable of inducing ICD.
• To identify potent anticancer agents with improved ICD-inducing efficiency.
• To elucidate the mechanism of ICD induced by the novel compounds.

Main Methods:

• Synthesis of a library of benzo[a]quinolizinium-based Au(i) complexes via intramolecular amino-auration.
• Screening of 40 candidates to identify lead compounds.
• Evaluation of ICD induction, DAMPs generation, and cancer cell phagocytosis.
• Mechanistic studies involving oxidative stress and mitophagy in A549 cells.

Main Results:

• BQ-AurIPr, a novel redox-active Au(i) complex, was identified with potent anticancer properties.
• BQ-AurIPr efficiently triggered Damage-Associated Molecular Patterns (DAMPs), hallmarks of ICD.
• The compound demonstrated superior ICD-inducing efficiency compared to FDA-approved drugs.
• BQ-AurIPr enhanced cancer cell immunogenicity and phagocytosis by immune cells.

Conclusions:

• BQ-AurIPr is a promising novel gold(I) complex for inducing immunogenic cell death.
• The compound's mechanism involves inducing mitochondrial oxidative stress and mitophagy.
• BQ-AurIPr holds potential for enhancing cancer immunotherapy and clinical outcomes.