基于的MX酶的瘤微环境驱动的结构转化,以扩大用于多模式瘤治疗的氧化应激
Hai Zhu1,2, Tinghua Li3, Xinhao Peng1
1Department of Oncology, Affiliated Hospital of Southwest Jiaotong University/The Third People's Hospital of Chengdu, Chengdu, 610031, China.
工程化瓦纳碳化物MX酶在瘤微环境中转化,放大氧化应激,用于增强癌症治疗. 这种新的方法提高了多模式瘤治疗的疗效.
科学领域:
- 生物材料科学 生物材料科学
- 纳米技术 纳米技术
- 癌症治疗 癌症治疗
背景情况:
- MX酶在瘤治疗方面表现有前途,但在瘤微环境 (TME) 中的催化效率面临挑战.
- 低于最佳的动力学和效率限制了MX酶在TME中的治疗潜力.
研究的目的:
- 设计瓦纳碳化物MX酶 (TVMz),利用TME特征进行结构转化和增强催化活性.
- 通过通过MXenzyme的结构变化增强氧化应激,开发一种多式瘤治疗策略.
主要方法:
- 设计的氨酸涂层TVMz (HTVMz) 为稳定性和NIR-II激光响应.
- 利用TME特性和NIR-II辐射诱导HTVMz转化为氧化瓦纳纳米酶 (VOx).
- 研究了VOx介导的活性氧物种 (ROS) 放大和破坏细胞氧化还原稳定.
主要成果:
- HTVMz转化为具有增加表面积的超小VOx纳米酶,增强ROS再生.
- VOx放大了氧化应激,导致 lysosomal 透性增加,Endoplasmic reticulum 应激,并通过谷氨相互作用破坏了氧化还原平衡.
- 协同效应加速了瘤亡和铁亡,抑制了HSP90,并促进了瘤细胞死亡.
结论:
- 工程MX酶可以经历TME响应的结构转化,以增强催化疗法.
- 这一策略有效地放大了氧化应激,用于协同的多模式瘤细胞死亡.
- 该研究通过操纵MXenzyme结构和TME相互作用,为催化瘤治疗提供了一种新的方法.
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