一种MRI可见的纳米诊疗剂建立了自放大焦亡-STING-IFN-β回路以激活CD8 T细胞免疫
{"_":"An MRI-visible nanotheranostic establishes a self-amplifying pyroptosis-STING-IFN-β circuit for CD8 T cell immunoactivation.","sup":["+"]}
摘要(中文译文)
有效的肿瘤免疫治疗依赖于肿瘤内细胞毒性CD8 T细胞的充分浸润和持续功能发挥。在此，我们报道一种磁共振成像（MRI）可见的纳米诊疗剂，该制剂整合了氧化还原调节、炎性细胞死亡和先天免疫增敏，从而建立自放大的焦亡-STING-IFN-β回路以激活CD8 T细胞免疫。该纳米诊疗剂通过锰离子（Mn）催化的多酚氧化聚合构建，能够实现工程化的活性氧（ROS）生成和局部金属离子可利用性。在功能上，细胞内ROS触发caspase-3依赖的gasdermin E（GSDME）切割和焦亡，同时伴随的线粒体扰动增加胞质线粒体DNA（mtDNA）并敏化cGAS-STING通路以增强Mn介导的激活，导致IFN-β产生。IFN-β进一步促进树突状细胞成熟和CD8 T细胞致敏，而炎性焦亡放大mtDNA的可利用性，二者共同形成自放大的正反馈回路，放大抗肿瘤免疫。通过这一协调机制，该策略促进有效的CD8 T细胞浸润和记忆形成。由于其高纵向弛豫率，该纳米诊疗剂能够实现清晰的T加权MRI对比，并具有显著的肿瘤蓄积和延长滞留，支持影像引导的免疫治疗。这项工作提出了一种功能材料策略，将机制性免疫放大与诊断成像相结合，为可转化的免疫诊疗学提供了概念框架。
Abstract
Effective cancer immunotherapy relies on robust infiltration and sustained functionality of tumor-resident cytotoxic CD8 T cells. Here we report a magnetic resonance imaging (MRI)-visible nanotheranostic that integrates redox modulation, inflammatory cell death, and innate immune sensitization to establish a self-amplifying pyroptosis-STING-IFN-β circuit for CD8 T cell immunoactivation. The nanotheranostic is constructed through manganese ion (Mn)-catalyzed oxidative polymerization of polyphenols, enabling engineered reactive oxygen species (ROS) generation and localized metal ion availability. Functionally, intracellular ROS triggers caspase-3-dependent gasdermin E (GSDME) cleavage and pyroptosis, while concomitant mitochondrial perturbation increases cytosolic mitochondrial DNA (mtDNA) and sensitizes the cGAS-STING pathway to Mn-enhanced activation, resulting in IFN-β production. IFN-β further reinforces dendritic cells maturation and CD8 T cells priming, whereas inflammatory pyroptosis amplifies mtDNA availability, together forming a self-amplifying positive-feedback circuit that magnifies antitumor immunity. , this coordinated mechanism promotes effective CD8 T cells infiltration and memory formation. Owing to its high longitudinal relaxivity, the nanotheranostic enables clear T-weighted MRI contrast with pronounced tumor accumulation and prolonged retention, supporting imaging-guided immunotherapy. This work presents a functional materials strategy that couples mechanistic immune amplification with diagnostic imaging, offering a conceptual framework for translatable immunotheranostics.
如何引用
AMA
Pei Jing, Lan Wang, Xiaojuan Qiu, Liming Chen, Deyan Xie, Yongqi Yu, et al. {"_":"An MRI-visible nanotheranostic establishes a self-amplifying pyroptosis-STING-IFN-β circuit for CD8 T cell immunoactivation.","sup":["+"]}. Materials today. Bio. 2026; doi:10.1016/j.mtbio.2026.103338.
APA
Pei Jing, Lan Wang, Xiaojuan Qiu, Liming Chen, Deyan Xie, Yongqi Yu, et al (2026). {"_":"An MRI-visible nanotheranostic establishes a self-amplifying pyroptosis-STING-IFN-β circuit for CD8 T cell immunoactivation.","sup":["+"]}. Materials today. Bio. https://doi.org/10.1016/j.mtbio.2026.103338
GB/T 7714
Pei Jing, Lan Wang, Xiaojuan Qiu, Liming Chen, Deyan Xie, Yongqi Yu, et al. {"_":"An MRI-visible nanotheranostic establishes a self-amplifying pyroptosis-STING-IFN-β circuit for CD8 T cell immunoactivation.","sup":["+"]}[J]. Materials today. Bio, 2026 doi:10.1016/j.mtbio.2026.103338.
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