碳二硫化物在活细胞中的生物对等输送
Ruohan Zhao1, Yinghan Chen1, Yong Liang1
1State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, Chemistry and Biomedicine Innovation Center, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China.
Angewandte Chemie (International ed. in English)
|May 16, 2024
概括
我们开发了一种新的生物对等系统,用于控制细胞内的二硫化碳 (CS2) 释放. 这个系统揭示了CS2的存在.
科学领域:
- 生物化学 生物化学
- 毒理学 毒理学 毒理学
- 化学生物学 化学生物学
背景情况:
- 二硫化碳 (CS2) 是一种危险的环境污染物,毒性机制不明.
- 生物相容的CS2捐赠体的有限可用性阻碍了细胞内毒性研究.
研究的目的:
- 开发第一个生物对等的CS2输送系统,用于细胞内释放.
- 调查CS2诱导的肝毒性机制.
- 为了探索CS2与铜结合的潜在抗癌活性.
主要方法:
- 开发了一种"点击释放"系统,使用介质的1,3-thiazolium-5-thiolates (TATs) 和应变的环素 exo-BCN-OH.
- 实现了细胞内CS2释放.
- 研究了CS2诱导的肝毒性,重点是氧化应激,蛋白质毒性应激和依赖铜的细胞死亡.
主要成果:
- 成功证明了细胞内CS2释放.
- 确定CS2是一种绕过铜输送器的铜载体,加剧细胞死亡.
- 观察到铜补充会加剧CS2诱导的细胞损伤和恒常性损失.
结论:
- 开发的生物对等系统可以进行受控的细胞内CS2释放和毒性研究.
- CS2诱导的肝毒性包括氧化应激,蛋白质毒性应激和依赖铜的机制.
- CS2与铜的相互作用表明,有可能开发基于铜的抗癌疗法.
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