Radiotherapy (RT) is one of the major treatments for cancers and a promising initiator of immune response. Gold nanoparticles are a promising radiosensitizer. In this study, we sought to optimize the drug delivery efficiency of gold nanoparticles and explore their function in delivering stimulator of interferon genes (STING) agonists with or without RT. Gold nanoparticles covalent to MSA-2 (MSA-Au) were mixed with cRGD-modified neutrophil membranes to obtain M-Au@RGD-NM. We explored the treatment efficiency of M-Au@RGD-NM combined with RT. Immune cell regulation and STING pathway activation were detected. We successfully prepared M-Au@RGD-NM with significant tumor suppression by induction of ROS and the resulting DNA damage. In vivo dynamic imaging showed that M-Au@RGD-NM was mainly targeted to radiated tumors. Tumor-bearing mice showed significant tumor inhibition following a combination therapy. M-Au@RGD-NM significantly activated the STING pathway and regulated the whole-body immune response. Locally radiated tumors showed dendritic cells mature, CD8⁺ T cells upregulation, and M1 polarization, with systematic immune response demonstrated by CD8⁺ T cell infiltration in abscopal tumors. In this study, we synthesized M-Au@RGD-NM loading MSA-2. Following characterization, we found that RT-based M-Au@RGD-NM treatment achieved good antitumor effects, tumor RT enhancement, and induction of an immune response via STING activation.

中文翻译：

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由中性粒细胞膜包被的金纳米颗粒递送的 STING 激动剂与放疗协同抑制肿瘤


放疗 （RT） 是癌症的主要治疗方法之一，也是免疫反应的有前途的启动剂。金纳米颗粒是一种很有前途的放射增敏剂。在这项研究中，我们试图优化金纳米颗粒的药物递送效率，并探索它们在有或没有 RT 的情况下递送干扰素基因刺激剂 （STING） 激动剂的功能。将与 MSA-2 共价的金纳米颗粒 （MSA-Au） 与 cRGD 修饰的中性粒细胞膜混合以获得 M-Au@RGD-NM。我们探讨了 M-Au@RGD-NM 联合 RT 的治疗效果，检测免疫细胞调节和 STING 通路激活。我们成功制备了通过诱导 ROS 和由此产生的 DNA 损伤而具有显着肿瘤抑制的 M-Au@RGD-NM。体内动态成像显示 M-Au@RGD-NM 主要靶向放射肿瘤。荷瘤小鼠在联合治疗后表现出显着的肿瘤抑制。M-Au@RGD-NM 显著激活 STING 通路并调节全身免疫反应。局部放射肿瘤显示树突状细胞成熟、CD8⁺ T 细胞上调和 M1 极化，远隔肿瘤中 CD8⁺ T 细胞浸润证明了系统性免疫反应。在这项研究中，我们合成了 M-Au@RGD-NM 负载 MSA-2。根据表征，我们发现基于 RT 的 M-Au@RGD-NM 治疗实现了良好的抗肿瘤效果、肿瘤 RT 增强和通过 STING 激活诱导免疫反应。