金纳米颗粒通过差异调节吞噬作用直接杀伤癌细胞来增强抗体的作用。
Gold nanoparticles enhance antibody effect through direct cancer cell cytotoxicity by differential regulation of phagocytosis.
机构信息
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, 100190, China.
School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 100081, China.
出版信息
Nat Commun. 2021 Nov 4;12(1):6371. doi: 10.1038/s41467-021-26694-x.
Ramucirumab is the first FDA-approved monotherapy for advanced gastric cancer. In this study, Ramucirumab (Ab) is attached to gold nanoparticles to enhance uptake efficiency. Gold nanoparticles can induce direct cytotoxic effects to cancer cells in the presence of Ab, while individual Ab or gold nanoparticles don't have such an effective anticancer effect even at extremely high concentrations. Proteomic and transcriptomic analyses reveal this direct cytotoxicity is derived predominantly from Ab-mediated phagocytosis. High affinity immunoglobulin gamma Fc receptor I shows differential up-regulation in gastric cancer cells treated by these nanodrugs compared with Ab, especially for Ab with gold nanorods. Simplified and powerful designs of smart nanoparticles are highly desired for clinical application. The enhancement of Ab accumulation with a simple composition, combined with direct cytotoxic effects specific to cancer cells brought improved therapeutic effects in vivo compared with Ab, which can promote further clinical application of gold nanomaterials in the diagnosis and therapeutics of gastric cancer.
雷莫芦单抗是首个被 FDA 批准用于治疗晚期胃癌的单克隆抗体药物。在这项研究中，雷莫芦单抗（Ab）被连接到金纳米粒子上，以提高摄取效率。金纳米粒子在存在 Ab 的情况下可以对癌细胞产生直接的细胞毒性作用，而单独的 Ab 或金纳米粒子即使在极高浓度下也没有这种有效的抗癌作用。蛋白质组学和转录组学分析表明，这种直接的细胞毒性主要来自 Ab 介导的吞噬作用。与 Ab 相比，高亲和力免疫球蛋白γ Fc 受体 I 在这些纳米药物处理的胃癌细胞中表现出不同程度的上调，尤其是 Ab 与金纳米棒结合时。简化和强大的智能纳米粒子设计是临床应用所需要的。与 Ab 相比，用简单的成分增强 Ab 积累，并结合对癌细胞的直接细胞毒性作用，可在体内提高治疗效果，这可以促进金纳米材料在胃癌的诊断和治疗中的进一步临床应用。
Zotero 插件