色素向的ROS响应的基于氧化石墨烯的药物递送系统,以克服瘤DOX耐药性
Fengzhu Yang1, Jintao Deng1, Xinyu Yu1
1School of Life Science and Medicine, Shandong University of Technology, Zibo, Shandong 255000, China.
Colloids and surfaces. B, Biointerfaces
|January 14, 2026
概括
一种新的纳米药物输送系统 (Dp/DGPP) 通过增加反应性氧物种 (ROS) 来破坏溶酶体来克服瘤溶酶体的抗性. 这增强了多克索鲁比 (DOX) 的释放和对抗耐药癌细胞的疗效.
科学领域:
- 生物医学工程 生物医学工程
- 纳米技术 纳米技术
- 癌症治疗 癌症治疗
背景情况:
- 多克索鲁比 (DOX) 的溶酶体隔离限制了其在耐药瘤中的有效性.
- 瘤细胞利用溶酶体机制抵抗化疗,降低细胞内药物度.
研究的目的:
- 开发一种纳米药物输送系统 (Dp/DGPP),以克服瘤中的溶酶体耐药性.
- 为了增强DOX在耐药癌细胞中的治疗效果.
主要方法:
- 使用石墨烯氧化物---DOX,聚乙烯胺-多F127和DP44mT的DP/DGPP构建.
- 研究了ROS依赖的DOX释放及其对溶酶体膜透性的影响.
- 评估了细胞毒性,细胞吸收和对Pgp,LC3-II和P62蛋白质表达的影响.
- 在异种移植模型中评估了体内瘤抑制.
主要成果:
- Dp/DGPP显示显著的ROS依赖DOX释放和对MCF-7/ADR细胞增强的细胞毒性 (IC50=6.71μM).
- 观察到细胞内DOX积累增加 (1.5倍) 和溶酶体功能障碍.
- Dp/DGPP治疗减少了Pgp表达,同时增加了LC3-II和P62,表明自流被阻塞.
- 在体内MCF-7/ADR瘤中达到70%的抑制率.
结论:
- 通过利用ROS放大,DP/DGPP系统有效地克服了瘤 lysosomal 抵抗.
- 这种纳米药物输送策略增强了DOX的有效性,并促进了癌细胞的死亡.
- Dp/DGPP为治疗耐DOX癌症提供了一种有前途的方法.
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