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装有SAHA的RGD修改金纳米粒子通过抑制HIF-1α-VEGF信号来重塑低毒炎症微环境,以增强NSCLC中的放射敏感性.

Junqi Lin1, Xiaoming Huang1, Xizhen Wang1

  • 1Department of Respiratory Medicine, People's Hospital of Longhua Shenzhen, Shenzhen, 518109, People's Republic of China.

International journal of nanomedicine
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概括

这项研究开发了RGD功能化金纳米颗粒,加载SAHA (suberoylanilide hydroxamic acid) 来增强非小细胞肺癌 (NSCLC) 的辐射敏感性. RGD-AuNPs-SAHA有效地减少了瘤生长和改善了治疗结果.

关键词:
这是一种RGD.金纳米颗粒的金子纳米颗粒低毒的微环境是什么非小细胞肺癌的肺癌.辐射敏感性 辐射敏感性

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科学领域:

  • 生物医学工程 生物医学工程
  • 纳米技术纳米技术
  • 在瘤学瘤学.

背景情况:

  • 非小细胞肺癌 (NSCLC) 仍然是癌症相关死亡的主要原因.
  • 瘤微环境中的缺氧促进了放射电阻和转移.
  • 有针对性的药物输送系统对于提高癌症治疗疗效至关重要.

研究的目的:

  • 为了合成和表征RGD功能化金纳米颗粒 (AuNPs) 装载SAHA (suberoylanilide酸).
  • 通过向缺氧来评估RGD-AuNPs-SAHA作为NSCLC放射敏感剂的潜力.
  • 评估治疗疗效和 in vitro 和 in vivo 的作用机制.

主要方法:

  • 通过酸盐还原和硫醇-黄金结合合成RGD-AuNPs-SAHA.
  • 使用DLS,TEM,UV-Vis,HPLC,FTIR,TGA和XPS进行表征.
  • 细胞吸收,生物分布,药物释放,瘤体积,细胞因子分析,氧化应激标志物和分子分析 (IHC,IF,西斑,RT-PCR) 的体外和体内评估.
  • 使用TUNEL和γ-H2AX染色对DNA损伤和亡的评估.

主要成果:

  • RGD-AuNPs-SAHA表现出均的大小 (~20 nm) 具有高SAHA封装 (85.2%) 和响应pH的释放.
  • 在体内研究表明,瘤体积减少了60%和调节炎性细胞因子.
  • 氧化应激标志物的显著改善和低氧信号蛋白 (HIF-1α,VEGF) 的抑制被观察到.
  • 亡和DNA损伤标记的增加表明放射敏感性增强.

结论:

  • 在NSCLC中,RGD-AuNPs-SAHA有效地重塑了缺氧瘤微环境.
  • 开发的纳米药物减轻了氧化应激,并抑制了前瘤源信号.
  • 这种方法提供了一个有前途的策略,以提高辐射敏感性和改善NSCLC的辐射治疗结果.