Immunogenic cell death (ICD) is a promising direction of cancer immunotherapy in in most carcinomas, including hepatocellular carcinoma (HCC). A series of novel Au(I) complexes derived from 4,5-diarylimidazole, containing glycyrrhetinic acid (GA) as an efficient targeting ligand for HCC is herein design and synthesize. Of these, complex 4c exhibits the excellent the effectiveness for tumor targeting and antitumor activity, induce the occurrence of ICD in HCC cells. Further, 4c can effectively inhibit TrxR enzyme activity and increase reactive oxygen species (ROS), resulting in redox homeostasis disorder, mediate mitochondrial dysfunction and endoplasmic reticulum stress (ERS), result in the characteristic discharge of damage-associated molecular patterns (DAMPs) in HCC cells. More importantly, 4c shows a great ICD-inducing effects in a vaccination mouse model and leads to activate antitumor immunity in tumor-bearing C57/BL6 mouse model. Accordingly, ICD induction and chemotherapeutic effects of 4c can also be seen in human primary liver cancer organoids. In conclusion, we show the potential of Au(I) complex with HCC-targeted capabilities for effective tumor immunotherapy.

Tumor-targeting Au(I) complex which induces immunogenic cell death in hepatocellular carcinoma

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ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.