Targeting Lymph Node Sinus Macrophages to Inhibit Lymph Node Metastasis
Targeting Lymph Node Sinus Macrophages to Inhibit Lymph Node Metastasis
复制标题
靶向淋巴结窦巨噬细胞抑制淋巴结转移
DOI：
10.1016/j.omtn.2019.04.016
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发表时间：
2019-06-07
影响因子：
8.8
通讯作者：
Huang, Zhen
中科院分区：
文献类型：
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作者：
Hu, Junging;Xu, Jinhao;Huang, Zhen
淋巴结是重要的外周免疫器官，在其中发生许多重要的免疫应答。在淋巴转移的过程中，淋巴结也是肿瘤细胞必须通过的部位。因此，开发一种能够特异性地将免疫刺激药物转移到淋巴结中以阻断淋巴转移的药物递送系统是至关重要的。本研究以阳离子琼脂糖（C-agarose）和CpG寡核苷酸为载体，构建了一种核酸药物传递系统。C-琼脂糖对淋巴结窦巨噬细胞表面的Siglec-1具有高亲和力，对靶向淋巴结具有高特异性。皮下植入C-琼脂糖+CpG凝胶可引起CpG在淋巴结窦巨噬细胞中的积聚，并在淋巴结中产生抗肿瘤免疫应答。在小鼠4 T1乳腺癌模型和B16 F10黑色素瘤模型中，C-琼脂糖+CpG凝胶处理降低了肿瘤引流淋巴结（TDLN）和肺转移结节中的转移大小，并抑制了肿瘤生长。在此基础上，本研究提出了非手术侵袭性淋巴结靶向免疫治疗的概念，可能为抗肿瘤转移提供新的途径。
Lymph nodes are important peripheral immune organs in which numerous important immune responses occur. During the process of lymphatic metastasis, lymph nodes are also sites through which tumor cells must pass. Therefore, it is essential to develop a drug delivery system that can specifically transfer immunostimulatory medicine into lymph nodes to block lymphatic metastasis. Here, we developed a nucleic acid drug delivery system containing cationic agarose (C-agarose) and CpG oligodeoxynucleotides. C-agarose has a high affinity for Siglec-1 on the surface of lymph node sinus macrophages, which have a high specificity for targeting lymph nodes. Subcutaneous implantation of C-agarose+CpG gel caused the accumulation of CpG in the lymph node sinus macrophages and generated antitumor immune responses in the lymph node. C-agarose+CpG gel treatment decreased the metastasis size in the tumor-draining lymph node (TDLN) and lung metastatic nodules and suppressed tumor growth in both a mouse 4T1 breast cancer model and a B16F10 melanoma model. On this basis, this study proposes a nonsurgical invasive lymph node targeting immunotherapy concept that may provide a new approach for antitumor metastasis.