Citation: Yanjun Cai, Yong Jiang, Yu Chen, Erzhuo Cheng, Yuan Gu, Yuwei Li, Qianqian Liu, Jian Zhang, Jifang Liu, Shisong Han, Bin Yang. Amplifying STING activation and immunogenic cell death by metal-polyphenol coordinated nanomedicines for enhanced cancer immunotherapy[J]. Chinese Chemical Letters, ;2025, 36(5): 110437. doi: 10.1016/j.cclet.2024.110437 shu

Amplifying STING activation and immunogenic cell death by metal-polyphenol coordinated nanomedicines for enhanced cancer immunotherapy

Yanjun Cai ^{a, 1} ,
Yong Jiang ^{a, 1} ,
Yu Chen ^{a, 1} ,
Erzhuo Cheng ^a ,
Yuan Gu ^a ,
Yuwei Li ^a ,
Qianqian Liu ^a ,
Jian Zhang ^a ,
Jifang Liu ^{b, *,} ,
Shisong Han ^{c, *,} ,
Bin Yang ^{a, b, *,}

a.
The Fourth Affiliated Hospital of Guangzhou Medical University, School of Biomedical Engineering, Guangzhou Medical University, Guangzhou 511436, China
b.
The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan 511518, China
c.
Zhuhai Institute of Translational Medicine, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai 519000, China

yzhbb2012@126.com

hanshs@qq.com

bin.yang@gzhmu.edu.cn

Received Date: 22 July 2024
Revised Date: 4 September 2024
Accepted Date: 9 September 2024
Available Online: 10 September 2024

Figures(6)

Ferroptosis in combination with immune therapy emerges as a promising approach for cancer therapy. Herein, dual-responsive metal-polyphenol coordinated nanomedicines were developed for pH/glutathione (GSH)-responsive synergistic ferroptosis and immunotherapy. Our innovative strategy involves the development of a manganese-polyphenol coordinated nanostructure, leveraging the biocompatibility of bovine serum albumin (BSA) as a template to encapsulate the anticancer drug sorafenib. The tumor microenvironment (pH/GSH) prompts the disassembly of MnO₂ and epigallocatechin gallate (EGCG), thereby releases the anticancer payload. Concurrently, MnO₂ acts to deplete intracellular GSH, which in turn suppresses glutathione peroxidase activity, leading to an accumulation of lipid peroxides with cell ferroptosis. Additionally, the release of Mn²⁺ ions bolster the cyclic guanosine monophosphlic acid (GMP)-adenosine monophosphlic acid (AMP) synthase-stimulator of interferon gene (cGAS-STING) pathway, which, in conjunction with the immunogenic cell death (ICD) effect induced by tumor cell apoptosis, significantly promotes dendritic cell (DC) maturation and enhances the presentation of tumor antigens. This successively ignites a robust innate and adaptive immune response. Both in vitro and in vivo experiments have demonstrated that the concurrent administration of ferroptosis-inducing and immune-stimulating therapies can significantly inhibit tumor growth.
- Immunotherapy,
- STING activation,
- Ferroptosis,
- Immunogenic cell death,
- Metal-polyphenol nanomedicines
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沈阳化工大学材料科学与工程学院沈阳 110142