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聚羟化富勒醇调节巨噬细胞进行癌症过继免疫治疗,极大地抑制肿瘤转移。

Polyhydroxylated fullerenols regulate macrophage for cancer adoptive immunotherapy and greatly inhibit the tumor metastasis.

机构信息

Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, China; Center for Nanochemistry, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.

Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, China.

出版信息

Nanomedicine. 2016 May;12(4):945-954. doi: 10.1016/j.nano.2015.11.021. Epub 2015 Dec 28.

Abstract

UNLABELLED

Adoptive immunotherapy is a highly effective approach for cancer treatment. Several potential adoptive immunotherapies have high (though reversible) toxicities with disappointing results. Polyhydroxylated fullerenols have been demonstrated as promising antitumor drugs with low toxicities. In this study, we investigate whether polyhydroxylated fullerenols (C60(OH)22 and Gd@C82(OH)22) contribute to cancer immunotherapy by regulating macrophages. Our results show that fullerenols treatment enhances mitochondrial metabolism, phagocytosis and cytokine secretion. Moreover, activated macrophages inhibit the growth of several cancer cell types. It is likely that this inhibition is dependent on an NF-κB-mediated release of multiple cytokines. Using a lung metastasis model, we also show that autologous macrophages greatly suppress cancer cell metastasis to lung when they are activated by C60(OH)22 and Gd@C82(OH)22. More importantly, Gd@C82(OH)22 are shown to have stronger ability than C60(OH)22 to improve the macrophage function, which shed light on the rational design for nanomedicine and clinical application.

FROM THE CLINICAL EDITOR

The interest in the use of immunotherapy in cancer has rekindled recently. However, many approaches have shown disappointing results. In this study, the authors investigated the effects of polyhydroxylated fullerenol nanoparticles on regulating macrophages for immunotherapy. These positive findings may point a novel way to cancer treatment.

摘要

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过继免疫疗法是一种治疗癌症的高效方法。几种潜在的过继免疫疗法具有较高(尽管是可逆的)毒性和令人失望的结果。多羟基富勒醇已被证明是具有低毒性的有前途的抗肿瘤药物。在这项研究中,我们研究了多羟基富勒醇(C60(OH)22 和 Gd@C82(OH)22)是否通过调节巨噬细胞来促进癌症免疫疗法。我们的结果表明,富勒醇处理增强了线粒体代谢、吞噬作用和细胞因子分泌。此外,激活的巨噬细胞抑制了几种癌细胞类型的生长。这种抑制可能依赖于 NF-κB 介导的多种细胞因子的释放。使用肺转移模型,我们还表明,当 C60(OH)22 和 Gd@C82(OH)22 激活时,自体巨噬细胞极大地抑制了癌细胞向肺部的转移。更重要的是,与 C60(OH)22 相比,Gd@C82(OH)22 显示出更强的增强巨噬细胞功能的能力,这为纳米医学和临床应用的合理设计提供了思路。

临床编辑按语

最近,人们对癌症免疫疗法的兴趣重新燃起。然而,许多方法的结果令人失望。在这项研究中,作者研究了多羟基富勒醇纳米颗粒对调节巨噬细胞进行免疫治疗的影响。这些积极的发现可能为癌症治疗提供了一种新的途径。

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