Pt(II)-NHC Complex Induces ROS-ERS-Related DAMP Balance to Harness Immunogenic Cell Death in Hepatocellular Carcinoma.

Immunogenic cell death (ICD) can engage a specific immune response and establish a long-term immunity in hepatocellular carcinoma (HCC). Herein, we design and synthesize a series of Pt(II)--heterocyclic carbene (Pt(II)-NHC) complexes derived from 4,5-diarylimidazole, which show strong anticancer activities . Among them, displays much higher anticancer activities than cisplatin and other Pt(II)-NHC complexes, especially in HCC cancer cells. In addition, we find that is a type II ICD inducer, which can successfully induce endoplasmic reticulum stress (ERS) accompanied by reactive oxygen species (ROS) generation and finally lead to the release of damage-associated molecular patterns (DAMPs) in HCC cells. Importantly, shows a great anti-HCC potential in a vaccination mouse model and leads to the immune cell activation in the CCl-induced liver injury model.