The effect of Gd@C82(OH)22 nanoparticles on the release of Th1/Th2 cytokines and induction of TNF-α mediated cellular immunity
The effect of Gd@C82(OH)22 nanoparticles on the release of Th1/Th2 cytokines and induction of TNF-α mediated cellular immunity
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DOI：
10.1016/j.biomaterials.2009.04.001
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发表时间：
2009-08-01
期刊：
影响因子：
14
通讯作者：
Chen, Chunying
中科院分区：
文献类型：
--
作者：
Liu, Ying;Jiao, Fang;Chen, Chunying
众所周知，免疫反应的下调可能与癌症或传染病的发生、发展和预后有关。因此，上调体内免疫反应是临床治疗的理想策略。在这里，我们报道了多羟基金属富勒烯醇（Gd@C-82(OH)(22)）由于体内和体外观察到的免疫调节作用而具有可用于抗癌治疗的生物医学功能。我们发现金属富勒烯醇可以抑制肿瘤的生长，并对T细胞和巨噬细胞表现出特异性的免疫调节作用。这些效应包括使细胞因子平衡偏向 Th1（1 型辅助性 T 细胞）细胞因子，减少血清样本中 Th2 细胞因子（IL-4、IL-5 和 IL-6）的产生，以及增加 Th1 细胞因子（IL-2、IFN-γ 和 TNF-α）的产生。这种纳米材料对免疫系统的调节表现出剂量依赖性行为：在低浓度下，Gd@C-82(OH)(22)纳米颗粒对体外免疫细胞的活性略有影响，而在高浓度下，它们显着增强免疫反应，刺激免疫细胞释放更多细胞因子，帮助消除异常细胞。 Gd@C-82(OH)(22) 纳米粒子刺激 T 细胞和巨噬细胞释放大量的 TNF-α，这在细胞免疫过程中发挥着关键作用。 Gd@C-82(OH)(22)纳米颗粒在抑制小鼠肿瘤生长方面比一些临床抗癌药物更有效，但副作用可以忽略不计。高抗癌活性的潜在机制可能归因于这种水溶性纳米材料有效触发宿主免疫系统清除肿瘤细胞。 (C) 2009 Elsevier Ltd. 保留所有权利。
It is known that down-regulation of the immune response may be associated with the progenesis, development and prognosis of cancer or infectious diseases. Up-regulating the immune response in vivo is therefore a desirable strategy for clinical treatment. Here we report that poly-hydroxylated metallofullerenol (Gd@C-82(OH)(22)) has biomedical functions useful in anticancer therapy arising from immunomodulatory effects observed both in vivo and in vitro. We found that metallofullerenol can inhibit the growth of tumors, and shows specific immunomodulatory effects on T cells and macrophages. These effects include polarizing the cytokine balance towards Th1 (T-helper cell type 1) cytokines, decreasing the production of Th2 cytokines (IL-4, IL-5 and IL-6), and increasing the production of Th1 cytokines (IL-2, IFN-gamma and TNF-alpha) in the serum samples. Immune-system regulation by this nanomaterial showed dose-dependent behavior: at a low concentration, Gd@C-82(OH)(22) nanoparticles slightly affected the activity of immune cells in vitro, while at a high concentration, they markedly enhanced immune responses and stimulated immune cells to release more cytokines, helping eliminate abnormal cells. Gd@C-82(OH)(22) nanoparticles stimulated T cells and macrophages to release significantly greater quantities of TNF-alpha, which plays a key role in cellular immune processes. Gd@C-82(OH)(22) nanoparticles are more effective in inhibiting tumor growth in mice than some clinical anticancer drugs but have negligible side effects. The underlying mechanism for high anticancer activity may be attributed to the fact that this water-soluble nanomaterial effectively triggers the host immune system to scavenge tumor cells. (C) 2009 Elsevier Ltd. All rights reserved.