在模仿性骨微环境中杀死癌细胞的酶响应性"无药"酸酶
Meihui Yi1, Fengbin Wang2, Weiyi Tan1
1Department of Chemistry, Brandeis University, 415 South Street, Waltham, Massachusetts 02453, United States.
Journal of the American Chemical Society
|July 18, 2022
概括
新的杆芳香分子向骨转移中的酸酶. 这种方法通过形成纳米管结构在模拟骨环境中杀死癌细胞.
科学领域:
- 生物化学
- 材料科学
- 癌症学
背景情况:
- 骨转移是癌症治疗的一个重大挑战.
- 针对性
- 没有药物
- 像酸酶这样的酶提供了治疗机会.
- 开发选择性向瘤微环境的新分子至关重要.
研究的目的:
- 为酸酶设计和合成具有酶反应的刚性棒芳物质.
- 在骨转移模型中评估这些分子杀死癌细胞的有效性.
- 阐明这些分子的自我组装机制和结构特征.
主要方法:
- 合成pBP-NBD (1P) 通过化和结合二糖 (NBD) 到二碳酸盐 (BP).
- 与转移性抵抗割的前列腺癌细胞 (mCRPC) 和骨质细胞模仿细胞 (Saos2) 的共同培养实验.
- 电子显微镜 (Cryo-EM) 用于以原子分辨率确定纳米管结构.
主要成果:
- 在共培养中,pBP-NBD (1P) 有效地杀死mCRPC和Saos2细胞.
- 1P迅速进入Saos2细胞并向内质网膜 (ER).
- 同培养增强了mCRPCs的1P吸收;冷EM显示相同的螺旋纳米管包装通过pi堆叠相互作用稳定.
结论:
- 酶敏感的刚性棒芳基可以作为酸酶的基质,在骨转移的微环境中消除癌细胞.
- 这些分子的自组装纳米管结构以原子分辨率为特征.
- 这项工作扩展了针对TME的酶指令自组装 (EISA) 基板的分子工具包.
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