Ferroptosis-inducing inorganic arsenic(II) sulfide nanocrystals enhance immune activation

Jingyi Zhang; Yue Qin; Zhicheng Wang; Wei Zhang; Shengjin Liu; Wei Wei; Xiuxiu Wang; Jing Zhao

doi:10.1007/s12274-023-5617-y

Nano Research 2023, 16(7): 9760-9767 https://doi.org/10.1007/s12274-023-5617-y

Research Article | Issue | Published: 25 March 2023

Ferroptosis-inducing inorganic arsenic(II) sulfide nanocrystals enhance immune activation

Show Author's Information Hide Author's Information Jingyi Zhang^¹, Yue Qin^¹, Zhicheng Wang^², Wei Zhang^², Shengjin Liu^³, Wei Wei^²(

), Xiuxiu Wang^¹(

), Jing Zhao^¹(

)

1Chemistry and Biomedicine Innovation Center (ChemBIC), State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China

2School of Life Sciences, Nanjing University, Nanjing 210023, China

3College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China

Keywords:

ferroptosis, immune activation, arsenic sulfide, immunogenic cell death (ICD)

Topics:

Cell death

Cite this article:

Zhang J, Qin Y, Wang Z, et al. Ferroptosis-inducing inorganic arsenic(II) sulfide nanocrystals enhance immune activation. Nano Research, 2023, 16(7): 9760-9767. https://doi.org/10.1007/s12274-023-5617-y

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Abstract

Arsenic(II) sulfide is a stable inorganic arsenic compound with a different valence from arsenic trioxide, and has been widely applied to treat various diseases with low toxic side effects for a long time. However, its low solubility and complicated formulations restrict its further applications in modern medical industry. Meanwhile, as the tumour with the highest incidence rate among women, the low recurrence risk of breast cancer has been confirmed to be closely related to the high infiltration of immune cells. Herein, we synthesized and filtered novel biocompatible PEGylated arsenic(II) sulfide nanocrystals AsS@PEG with a size of 93.14 ± 0.49 nm by the gel method, which displayed excellent anticancer and immune activation activity in breast cancer model. Proteomic analysis suggested that the AsS@PEG induce ferroptosis in cancer cells and further activate antitumour immune responses via B-cell lymphoma 9-like (BCL9L) protein inhibition. Furthermore, mechanism studies revealed notable glutathione peroxidase 4 (GPX4) downregulation in cancer cells, dendritic cells (DCs) maturation and subsequent effector CD8⁺ T-cells production induced by the AsS@PEG in the tumour microenvironment. This study highlights biocompatible arsenic(II) sulfide nanocrystals that induce ferroptotic cell death and activate antitumour immune responses, providing insights into the path towards the immunotherapy assisted chemotherapy for breast cancer.

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About this article

Ferroptosis-inducing inorganic arsenic(II) sulfide nanocrystals enhance immune activation

Show Author's information Hide Author's Information Jingyi Zhang^¹, Yue Qin^¹, Zhicheng Wang^², Wei Zhang^², Shengjin Liu^³, Wei Wei^²(

), Xiuxiu Wang^¹(

), Jing Zhao^¹(

)

1Chemistry and Biomedicine Innovation Center (ChemBIC), State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China

2School of Life Sciences, Nanjing University, Nanjing 210023, China

3College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China

Abstract

Keywords: ferroptosis, immune activation, arsenic sulfide, immunogenic cell death (ICD)

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Acknowledgements

Publication history

Received: 16 November 2022

Revised: 18 February 2023

Accepted: 24 February 2023

Published: 25 March 2023

Issue date: July 2023

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 22207053, 91753121, 21872069, 51761135104, 21731004 and 91953201), the Shenzhen Basic Research Program (Nos. JCYJ20170413150538897 and JCYJ20180508182240106), the National Key R&D Program of China (Nos. 2017YFA0208200, 2016YFB0700600 and 2015CB659300), the Natural Science Foundation of Jiangsu Province (Nos. BK20220764, BK20180008 and BK20202004), The Fundamental Research Funds for the Central Universities, 2021 Strategic Research Project of the Science and Technology Commission of the Ministry of Education of China. We thank Shanghai Applied Protein Technology Co., Ltd., and OE Biotech Co., Ltd. (Shanghai, China) for providing technological assistance.