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

  • J Med Chem. 2022 Feb 10;65(3):1848-1866. doi: 10.1021/acs.jmedchem.1c01248.
Mianli Bian  1  2 ,  Rong Fan  1 ,  Zhibin Yang  1 ,  Yanan Chen  1 ,  Zhongren Xu  1 ,  Yunlong Lu  1 ,  Wukun Liu  1  3
Affiliations
  • 1. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Pharmacy, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, P. R. China.
  • 2. College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, P. R. China.
  • 3. State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210023, P. R. China.
PMID: 35025488 DOI: 10.1021/acs.jmedchem.1c01248
Abstract

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)-N-heterocyclic carbene (Pt(II)-NHC) complexes derived from 4,5-diarylimidazole, which show strong Anticancer activities in vitro. Among them, 2c displays much higher Anticancer activities than cisplatin and Other Pt(II)-NHC complexes, especially in HCC Cancer cells. In addition, we find that 2c 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, 2c shows a great anti-HCC potential in a vaccination mouse model and leads to the in vivo immune cell activation in the CCl4-induced liver injury model.

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