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.

二硫化二砷是一种与三氧化二砷不同化合价的稳定无机砷化合物，长期以来以低毒副作用广泛应用于各种疾病的治疗。然而，其低溶解度和复杂的配方限制了其在现代医药行业的进一步应用。同时，作为女性发病率最高的肿瘤，乳腺癌的低复发风险已被证实与免疫细胞的高浸润密切相关。在此，我们通过凝胶法合成并过滤了新型生物相容性聚乙二醇化砷 (II) 硫化物纳米晶体 AsS@PEG，其尺寸为 93.14 ± 0.49 nm，在乳腺癌模型中显示出优异的抗癌和免疫激活活性。蛋白质组学分析表明，AsS@PEG 在癌细胞中诱导铁死亡，并通过 B 细胞淋巴瘤 9 样 (BCL9L) 蛋白抑制进一步激活抗肿瘤免疫反应。此外，机制研究表明，在癌细胞、树突状细胞 (DC) 成熟和随后的效应子 CD8 中，谷胱甘肽过氧化物酶 4 (GPX4) 显着下调⁺ AsS@PEG 在肿瘤微环境中诱导的 T 细胞产生。本研究重点介绍了生物相容性砷 (II) 硫化物纳米晶体，该纳米晶体可诱导铁死亡细胞死亡并激活抗肿瘤免疫反应，从而为乳腺癌的免疫疗法辅助化疗提供了新途径。