• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nanotechnology >An albumin-bound drug conjugate of paclitaxel and indoleamine-2,3-dioxygenase inhibitor for enhanced cancer chemo-immunotherapy
【24h】

An albumin-bound drug conjugate of paclitaxel and indoleamine-2,3-dioxygenase inhibitor for enhanced cancer chemo-immunotherapy

机译：紫杉醇和吲哚胺-2,3-二氧基酶抑制剂的白蛋白结合药物缀合物，用于增强癌症化疗 - 免疫疗法

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Despite the promising target of immunosuppressive enzyme indoleamine-2,3-dioxygenase (IDO) for cancer immunotherapy, IDO blockade monotherapy does not show significant benefit to cancer patients in the clinic. Recent research has focused on the combinatorial therapy of the IDO inhibitor and the immune checkpoint blockade or chemotherapy. Here, we synthesize a drug conjugate methyltryptophan-paclitaxel (MP) by linking the IDO inhibitor, D-1-methyltryptophan (D-1MT), to the chemotherapeutic agent, paclitaxel (PTX), through an ester bond. MP exhibits a similar tubulin-stabilizing effect to PTX. Like PTX, MP binds to human serum albumin to form albumin-bound MP nanoparticles (MP NPs) with a particle size of similar to 115 nm in diameter. MP NPs significantly improve the tumor concentration of D-1MT due to the hydrolysis of MP in tumors. The codelivery of PTX and D-1MT offered by MP NPs in tumors significantly enhances the anti-tumor effect compared with the albumin-bound PTX NPs. Immune cell phenotyping reveals that MP NPs ameliorate the immune environment through increasing the number of the effector CD8(+) T cells, and decreasing the population of regulatory T cells and granulocyte-like myeloid-derived suppressor cells. These results prove that the design of the twin drug from the IDO inhibitor and PTX synergizes the anti-tumor effect and shows promise in clinical translation.
机译：尽管对癌症免疫疗法的免疫抑制酶-2,3-二恶英酶（IDO）的有希望的免疫抑制酶 - 2,3-二恶英酶（IDO），但IDO阻断单疗法对临床癌症患者没有显示出显着的益处。最近的研究专注于IDO抑制剂的组合治疗和免疫检查点梗死或化疗。这里，通过将IDO抑制剂，D-1-甲基对苯酚（D-1MT）连接到化学治疗剂，紫杉醇（PTX），通过酯键将药物缀合物甲基对甲基甘草 - 紫杉醇（MP）合成。 MP对PTX表现出类似的微管蛋白稳定作用。与PTX一样，MP与人血清白蛋白结合，形成白蛋白结合的MP纳米颗粒（MP NPS），粒度与直径相似的粒径。由于肿瘤中MP的水解，MP NPS显着提高D-1MT的肿瘤浓度。与白蛋白结合的PTX NPS相比，MP NPS提供的PTX和D-1MT的CODELIVE递送了肿瘤中的抗肿瘤作用显着提高了抗肿瘤作用。免疫细胞表型透露，MP NPS通过增加效应CD8（+）T细胞的数量和降低调节性T细胞和粒细胞样霉菌衍生的抑制细胞的群体来改善免疫环境。这些结果证明，来自IDO抑制剂和PTX的双药物的设计协同抗肿瘤效应并显示在临床翻译中的承诺。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号