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

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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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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.

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Authors and Affiliations

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

    Jingyi Zhang, Yue Qin, Xiuxiu Wang & Jing Zhao

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

    Zhicheng Wang, Wei Zhang & Wei Wei

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

    Shengjin Liu

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  1. Jingyi Zhang
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  4. Wei Zhang
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  6. Wei Wei
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Correspondence to Wei Wei, Xiuxiu Wang or Jing Zhao.

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

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  • DOI: https://doi.org/10.1007/s12274-023-5617-y

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