Liu Ying, Jiao Fang, Qiu Yang, Li Wei, Lao Fang, Zhou Guoqiang, Sun Baoyun, Xing Genmei, Dong Jinquan, Zhao Yuliang, Chai Zhifang, Chen Chunying
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190, China.
Biomaterials. 2009 Aug;30(23-24):3934-45. doi: 10.1016/j.biomaterials.2009.04.001. Epub 2009 Apr 28.
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.
众所周知，免疫反应的下调可能与癌症或传染病的发生、发展及预后相关。因此，在体内上调免疫反应是一种理想的临床治疗策略。在此，我们报告多羟基化金属富勒醇（Gd@C(82)(OH)(22)）具有免疫调节作用，在体内和体外均观察到其具有可用于抗癌治疗的生物医学功能。我们发现金属富勒醇可以抑制肿瘤生长，并对T细胞和巨噬细胞表现出特异性免疫调节作用。这些作用包括使细胞因子平衡向Th1（1型辅助性T细胞）细胞因子极化，减少Th2细胞因子（IL-4、IL-5和IL-6）的产生，并增加血清样本中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呈现剂量依赖性：在低浓度下，Gd@C(82)(OH)(22)纳米颗粒在体外对免疫细胞活性影响较小，而在高浓度下，它们显著增强免疫反应并刺激免疫细胞释放更多细胞因子，有助于消除异常细胞。Gd@C(82)(OH)(22)纳米颗粒刺激T细胞和巨噬细胞释放大量更多的TNF-α，TNF-α在细胞免疫过程中起关键作用。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，但副作用可忽略不计。其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地触发宿主免疫系统清除肿瘤细胞。
