• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>RSC Advances >An energy-blocking nanoparticle decorated with anti-VEGF antibody to reverse chemotherapeutic drug resistance
【24h】

An energy-blocking nanoparticle decorated with anti-VEGF antibody to reverse chemotherapeutic drug resistance

机译：用抗VEGF抗体装饰的能量阻断纳米粒子，以逆转化学治疗耐药性

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

Multi-drug resistance (MDR) of tumor cells has greatly hindered the therapeutic efficacy of chemotherapeutic drugs, resulting in chemotherapy failure, while overexpression of ATP-binding cassette (ABC) transporters in cell membranes is the leading cause of MDR. In this study, we reported novel self-assembled triphenylphosphine-quercetin-polyethylene glycol-monoclonal antibody nanoparticles (TQ-PEG-mAb NPs) for overcoming MDR primarily through mitochondrial damage to block ATP supply to ABC transporters both in vitro and in vivo. The doxorubicin (DOX)-loaded NPs (TQ/DOX-PEG-mAb) were composed of two drugs (TQ and DOX) and an outer shielding shell of the PEG-mAb conjugate. Besides, the outer shell could be acid-responsively detached to expose the positive charge of TQ inside the NPs to enhance cellular uptake. TQ was proved to effectively induce mitochondrial damage with increased ROS levels and depolarization of mitochondrial membrane potential (MMP), leading to prominently reduced ATP supply to ABC transporters. Moreover, the involvement of the anti-vascular endothelial growth factor (VEGF) mAb was not only for efficient targeting but also for combined therapy. Consequently, TQ/DOX-PEG-mAb showed that the internalized amount of DOX was largely improved while the efflux amount was dramatically inhibited on MCF-7/ADR cells, indicating excellent reversal of DOX resistance. Importantly, the growth of DOX-resistant breast tumors was significantly inhibited with no evident systemic toxicity. Therefore, the employment of TQ-PEG-mAb is believed to be a new approach to improve the efficacy of chemotherapeutic drugs in MDR tumors.
机译：肿瘤细胞的多药物抗性（MDR）大大阻碍了化学治疗药物的治疗效果，导致化疗衰竭，而在细胞膜中的ATP结合盒（ABC）转运蛋白的过度表达是MDR的主要原因。在这项研究中，我们报道了新型的自组装三苯基膦 - 槲皮素 - 聚乙二醇 - 聚乙二醇 - 单克隆抗体纳米颗粒（TQ-PEG-MAB NPS），用于克服MDR主要通过线粒体损伤，以阻止ATP供给在体外和体内对ABC转运蛋白。多柔比蛋白（DOX） - 加载的NPS（TQ / DOX-PEG-MAB）由两种药物（TQ和DOX）和PEG-MAB缀合物的外屏蔽壳组成。此外，外壳可以是酸性循环的，以暴露NPS内部TQ的正电荷以增强蜂窝摄取。证明TQ有效地诱导线粒体损伤随着线粒体膜电位（MMP）的增加和线粒体膜电位（MMP）的去极化，导致ABC转运蛋白的ATP供应占据突出减少。此外，抗血管内皮生长因子（VEGF）MAb的参与不仅用于有效靶向，还用于组合治疗。因此，TQ / DOX-PEG-MAb表明，在MCF-7 / ADR细胞上显着抑制了流出量的情况下，DOX的内化量大幅提高，表明DOX抗性的优异逆转。重要的是，Dox抗性乳腺肿瘤的生长显着抑制了没有明显的全身毒性。因此，认为TQ-PEG-MAb的就业是提高MDR肿瘤中化学治疗药物疗效的新方法。

著录项

  • 来源
    《RSC Advances》 |2019年第21期|共14页
  • 作者

    Gu Liu-Qing; Cui Peng-Fei; Xing Lei; He Yu-Jing; Chang Xin; Zhou Tian-Jiao; Liu Yu; Li Ling; Jiang Hu-Lin;

  • 作者单位

    China Pharmaceut Univ Dept Pharmaceut State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ Dept Pharmaceut State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ Dept Pharmaceut State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ Dept Pharmaceut State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ Dept Pharmaceut State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ Dept Pharmaceut State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ Sch Life Sci &

    Technol Dept Biochem Nanjing 210009 Jiangsu Peoples R China;

    Southeast Univ Zhongda Hosp Dept Endocrinol Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ Dept Pharmaceut State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
  • 关键词

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