基于通过瘤膜涂层的CB-839/IR-780纳米粒子阻断谷氨酶的改进光动力疗法
Zhiyan Li1,2, Xianghui Li1,2,3, Yanjun Lu1
1Division of Gastric Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.
Small (Weinheim an der Bergstrasse, Germany)
|October 24, 2023
概括
这项研究引入了一种新的纳米粒子,通过向谷氨胺代谢来增强光动力疗法 (PDT). 这种方法克服了瘤缺氧,并增强了活性氧物种 (ROS) 的致命作用,以改善癌症治疗.
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:
- 光动力学疗法 (PDT) 的疗效通常受到瘤缺氧和减少性物质的限制.
- 谷氨胺代谢在癌细胞生存和氧化还原平衡中起着至关重要的作用.
- 现有的PDT策略难以克服瘤微环境带来的挑战.
研究的目的:
- 开发一种新的纳米粒子 (IRCB@M),通过向谷氨酸代谢来增强PDT.
- 研究纳米粒子在阻断有氧呼吸和减少细胞抗氧化剂方面的双重作用.
- 在体内评估增强型PDT对胃癌的治疗疗效.
主要方法:
- 构建一个纳米粒子 (IRCB@M) 封装一个光敏化剂 (IR-780) 和一个谷氨酸酶抑制剂 (CB-839).
- 癌细胞膜涂层用于同源向.
- 在体外和体内评估谷氨胺代谢干预,低氧缓解和抗氧化剂水平降低.
- 在胃癌模型中评估PDT的疗效和抗瘤作用.
主要成果:
- IRCB@M纳米粒子成功地阻断了谷氨胺代谢,缓解了瘤缺氧.
- 干预导致尼古丁胺胺氨基二核酸盐 (NADPH) 和减少的谷氨 (GSH) 的水平降低.
- 这些变化放大了IR-780介导的光动力学治疗的致命效果,在体内显示出显著的抗瘤活性.
结论:
- 向谷氨胺代谢提供了一种新的策略,以提高PDT的疗效.
- 开发的纳米粒子 (IRCB@M) 有效地克服了瘤微环境的局限性,以改善癌症治疗.
- 这种方法为ROS依赖疗法,包括PDT提供了一个有前途的新概念.
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