钌(II)配合物通过诱导焦亡和免疫原性细胞死亡并激活cGAS-STING通路增强抗乳腺癌免疫应答
Ruthenium(II) complex enhances anti-breast cancer immune responses by inducing pyroptosis and immunogenic cell death while activating the cGAS-STING pathway.
摘要(中文译文)
癌症免疫治疗通过广谱恶性肿瘤中展现出强效抗肿瘤疗效和持久治疗反应，已彻底改变了肿瘤治疗格局。在本研究中，合理设计、合成并系统表征了三种新型Ru(II)配合物（Ru1、Ru2和Ru3）。体外抗肿瘤评价表明，三种Ru(II)配合物均对癌细胞产生显著的细胞毒性作用。其中，Ru3表现出更优越的生物活性，通过内吞介导途径快速进入MCF-7细胞，同时在线粒体和内质网中蓄积。机制研究揭示，Ru3诱导显著的S期细胞周期阻滞，随后触发肿瘤细胞焦亡性细胞死亡。更重要的是，Ru3有效启动免疫原性细胞死亡（ICD）并激活cGAS-STING信号通路，从而放大抗肿瘤免疫应答。后续体内研究进一步表明，Ru3显著提高小鼠树突状细胞与CD8 T细胞的比例，增强效应T细胞活性，并降低免疫抑制性调节性T细胞（T）的比例，进而激活宿主抗肿瘤免疫。总体而言，这些发现表明Ru3将直接杀肿瘤活性与免疫调节相结合，凸显其作为多功能Ru基抗癌候选药物用于癌症免疫治疗的巨大潜力。
Abstract
Cancer immunotherapy has revolutionized oncological treatment by exhibiting potent antitumor efficacy and durable therapeutic responses across a broad spectrum of malignancies. In the present study, three novel Ru(II) complexes (Ru1, Ru2, and Ru3) were rationally designed, synthesized, and systematically characterized. In vitro antitumor evaluations demonstrated that all three Ru(II) complexes exerted pronounced cytotoxic effects against cancer cells. Among them, Ru3 exhibited superior biological activity, rapidly entering MCF-7 cells through an endocytosis-mediated pathway while simultaneously accumulating within both mitochondria and the endoplasmic reticulum. Mechanistic investigations revealed that Ru3 induced significant S-phase cell cycle arrest and subsequently triggered pyroptotic cell death in tumor cells. More importantly, Ru3 effectively initiated immunogenic cell death (ICD) and activated the cGAS-STING signaling pathway, thereby amplifying antitumor immune responses. Subsequent in vivo studies further demonstrated that Ru3 markedly increased the ratio of dendritic cells to CD8 T cells, enhanced effector T-cell activity, and reduced the proportion of immunosuppressive regulatory T cells (T) in mice, which in turn activated host antitumor immunity. Collectively, these findings indicate that Ru3 integrates direct tumoricidal activity with immune modulation, highlighting its considerable potential as a multifunctional Ru-based anticancer candidate for cancer immunotherapy.
如何引用
AMA
Yuqing Zhang, Yuling Li, Jiaen Huang, Wenjing Yang, Jiaxi Chen, Xinxin Du, et al. Ruthenium(II) complex enhances anti-breast cancer immune responses by inducing pyroptosis and immunogenic cell death while activating the cGAS-STING pathway.. Bioorganic chemistry. 2026; doi:10.1016/j.bioorg.2026.110347.
APA
Yuqing Zhang, Yuling Li, Jiaen Huang, Wenjing Yang, Jiaxi Chen, Xinxin Du, et al (2026). Ruthenium(II) complex enhances anti-breast cancer immune responses by inducing pyroptosis and immunogenic cell death while activating the cGAS-STING pathway.. Bioorganic chemistry. https://doi.org/10.1016/j.bioorg.2026.110347
GB/T 7714
Yuqing Zhang, Yuling Li, Jiaen Huang, Wenjing Yang, Jiaxi Chen, Xinxin Du, et al. Ruthenium(II) complex enhances anti-breast cancer immune responses by inducing pyroptosis and immunogenic cell death while activating the cGAS-STING pathway.[J]. Bioorganic chemistry, 2026 doi:10.1016/j.bioorg.2026.110347.
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