诱导亡/亡的铁醇含有人工多的免疫细胞死亡的癌症细胞死亡
Jeong Ho Park1, Mun Sik Kim1, Do Hyun Yun1
1Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291, Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.
ACS applied bio materials
|December 4, 2023
概括
一种基于 thiazole 的新型多 (NS) 通过增加活性氧物种 (ROS) 和内质网膜 (ER) 应激,有效地诱导癌细胞的免疫细胞死亡 (ICD). 这种化合物显示出作为多功能癌症免疫治疗剂的潜力.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 免疫细胞死亡 (ICD) 是癌症免疫疗法的关键机制,涉及同时癌细胞死亡和损伤相关分子模式 (DAMP) 的释放.
- 增强型ICD依赖于增加的活性氧物种 (ROS) 和内 плазма网膜 (ER) 应激,其中ROS和谷氨酸 (GSH) 水平影响细胞死亡途径.
- 醇环结构因其作为抗癌剂的潜力而得到认可.
研究的目的:
- 设计和合成一种具有 thiazole 功能部分 (NS) 的新型正电荷细胞透聚.
- 研究NS在诱导癌细胞死亡和激活ICD中的作用机制.
- 评估NS作为度依赖的ICD诱导剂在癌症治疗中的潜力.
主要方法:
- 一个带正电荷的细胞透多的合成,其中包含一个 thiazole 功能部分 (NS).
- 通过癌细胞的直接透和内溶体逃逸来评估NS内部化.
- 评估NS诱导的线粒体去极化,ER压力,ROS生产和GSH耗尽.
- 分析DAMP信号释放和细胞死亡途径 (细胞亡到亡) 的转变,以应对不同的NS度.
主要成果:
- NS有效地穿透癌细胞,并以度依赖的方式触发线粒体脱极化和ER压力.
- NS显著增加ROS的产生,并耗尽GSH水平,导致ICD和DAMP释放的激活.
- 增加NS度促进细胞死亡从细胞亡转向亡.
结论:
- 合成的NS多是一种强大的免疫细胞死亡 (ICD) 诱导剂.
- NS通过ROS生成和ER压力激活癌细胞死亡,对细胞死亡途径产生可调节的影响.
- 作为癌症免疫治疗的多功能ICD诱导剂,NS显示出承诺,剂量根据癌症类型进行调整.
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