Even when treated with aggressive current therapies, patients with glioblastoma usually survive less than two years and exhibit a high rate of recurrence. CpG is an oligonucleotide that activates the innate immune system via Toll-like receptor 9 (TLR9) activation. Injection of CpG into glioblastoma tumors showed promise as an immunotherapy in mouse models but proved disappointing in human trials. One aspect of glioma that is not addressed by CpG therapy alone is the highly invasive nature of glioma cells, which is associated with resistance to radiation and chemotherapy. Here, we demonstrate that single-walled carbon nanotubes noncovalently functionalized with CpG (SWNT/CpG), which retain the immunostimulatory property of the CpG, selectively inhibit the migration of glioma cells and not macrophages without affecting cell viability or proliferation. SWNT/CpG also selectively decreased NF-κB activation in glioma cells, while activating macrophages by induction of the TLR9/NF-κB pathway, as we have previously reported. The migration inhibition of glioma cells was correlated with selective reduction of intracellular levels of reactive oxygen species (ROS), suggesting that an antioxidant-based mechanism mediates the observed effects. To the best of our knowledge, SWNT/CpG is the first nanomaterial that inhibits the migration of cancer cells while stimulating the immune system.

中文翻译：

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碳纳米管上的免疫刺激性CpG选择性抑制脑肿瘤细胞的迁移。

即使采用积极的当前疗法进行治疗，胶质母细胞瘤患者通常也可以存活不到两年，并且复发率很高。CpG是一种寡核苷酸，可通过Toll样受体9（TLR9）激活来激活先天免疫系统。向小鼠胶质母细胞瘤肿瘤中注射CpG有望在小鼠模型中作为一种免疫疗法，但在人体试验中却令人失望。单独用CpG疗法不能解决的神经胶质瘤的一方面是神经胶质瘤细胞的高度侵袭性，其与对放射线和化学疗法的抗性有关。在这里，我们证明了用CpG（SWNT / CpG）非共价功能化的单壁碳纳米管，它保留了CpG的免疫刺激特性，在不影响细胞活力或增殖的情况下，选择性抑制神经胶质瘤细胞而非巨噬细胞的迁移。正如我们先前报道的，SWNT / CpG还可以选择性地降低神经胶质瘤细胞中的NF-κB激活，同时通过诱导TLR9 /NF-κB途径激活巨噬细胞。胶质瘤细胞的迁移抑制与细胞内活性氧（ROS）水平的选择性降低相关，表明基于抗氧化剂的机制介导了观察到的作用。据我们所知，SWNT / CpG是第一种抑制癌细胞迁移同时刺激免疫系统的纳米材料。胶质瘤细胞的迁移抑制与细胞内活性氧（ROS）水平的选择性降低相关，表明基于抗氧化剂的机制介导了观察到的作用。据我们所知，SWNT / CpG是第一种抑制癌细胞迁移同时刺激免疫系统的纳米材料。胶质瘤细胞的迁移抑制与细胞内活性氧（ROS）水平的选择性降低相关，表明基于抗氧化剂的机制介导了观察到的作用。据我们所知，SWNT / CpG是第一种抑制癌细胞迁移同时刺激免疫系统的纳米材料。