Citation: Qiuyue Lu, Min Shan, Jiaqi Yang, Zhongren Xu, Yueyue Lei, Wukun Liu. A dinuclear gold(I) complex with bis(N-heterocyclic carbene) ligands potentiated immune responses against liver cancer via ROS-driven endoplasmic reticulum stress and ferroptosis[J]. Chinese Chemical Letters, ;2025, 36(12): 110940. doi: 10.1016/j.cclet.2025.110940 shu

A dinuclear gold(I) complex with bis(N-heterocyclic carbene) ligands potentiated immune responses against liver cancer via ROS-driven endoplasmic reticulum stress and ferroptosis

Qiuyue Lu ^{a, 1} ,
Min Shan ^{a, b, 1} ,
Jiaqi Yang ^{a, 1} ,
Zhongren Xu ^{a, 1} ,
Yueyue Lei ^a ,
Wukun Liu ^{a, *,}

a.
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
b.
School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China

liuwukun0000@njucm.edu.cn

Received Date: 9 October 2024
Revised Date: 5 February 2025
Accepted Date: 10 February 2025
Available Online: 12 February 2025

Figures(5)

Superior neutral or cationic dinuclear gold(I) N-heterocyclic carbene (NHC) complexes with antitumor and tumor microenvironment regulation functions were developed by introducing an additional gold atom. The novel cationic dinuclear gold(I) complex 4a (BF5-Au) with bis-NHC ligands exhibited potent anti-liver cancer capacity in vitro and in vivo. The Hyper7 sensor was first used to analyze the sites of reactive oxygen species (ROS) generation by BF5-Au, showing that ROS were preferably generated in mitochondria and endoplasmic reticulum. Mechanism studies showed that BF5-Au could induce immunogenic cell death (ICD) via ROS-driven endoplasmic reticulum stress (ERS). However, targeting a single type of immune cell seems insufficient to reverse the immunosuppressive circumstances. Further investigation indicated that BF5-Au could enhance antitumor immune responses by inducing ferroptosis and polarizing macrophages to M1-like types. Overall, BF5-Au could inhibit tumor growth and remodel the tumor microenvironment via ROS-driven ERS and ferroptosis, which is expected to be a promising chemoimmunotherapy for cancer treatment.
- Dinuclear gold(I) NHC complexes,
- Liver cancer,
- Immune responses,
- Endoplasmic reticulum stress,
- Ferroptosis,
- Immunogenic cell death
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