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通过金属有机协调聚合物精确放大细胞内氧化风暴,增加抗癌免疫力

Shangfei Li¹, Xing Chen², Shuo Guan¹

¹Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, State Key Laboratory of Natural Medicines, Nanjing 210009, China.

|July 25, 2023

概括

这项研究引入了一种新型的光活性金属有机协调聚合物 (MOCP),可以放大氧化应激,诱导瘤细胞死亡并增强抗瘤免疫力,为癌症治疗提供了一种新的策略.

科学领域:

生物医学工程生物医学工程
纳米技术纳米技术
免疫学免疫学免疫学

背景情况:

氧化应激和活性氧物种 (ROS) 在调节瘤微环境和免疫反应方面发挥着关键作用.
准氧化应激路径是引起抗瘤免疫力的潜在策略.

研究的目的:

开发一种光活性金属有机协调聚合物 (MOCP),能够放大用于癌症治疗的细胞内氧化应激.
调查MOCP在诱导铁亡,免疫细胞死亡 (ICD) 和随后的抗瘤免疫力的有效性.

主要方法:

合成一个MOCP封装细胞毒性线粒激素 (MTX),光敏感的鲁复合物和GPX4-向siRNA (siGPX4) 的合成.
在体外和体内对MOCP的ROS生成,瘤积累和在670nmLED辐射下治疗效果的评估.
评估MOCP诱导铁亡,I型和II型ICD以及包括CD73封锁在内的免疫反应的能力.

主要成果:

MOCP显示MTX,Ru和siGPX4的封装效率高,血液循环延长,瘤积累增加.
对MOCPs的670nmLED辐射产生了显著的ROS,诱导了生物膜功能障碍,铁亡和免疫细胞死亡.
结合MOCP治疗与CD73阻断显著促进瘤回归,并通过增强抗原特异性免疫力来预防癌症复发.

结论:

开发的MOCP有效地放大氧化应激,触发多个细胞死亡途径和强大的抗瘤免疫力.
MOCPs作为协同癌症治疗的多功能平台,特别是与冷瘤的免疫检查点抑制剂相结合时.
这种方法对治疗晚期癌症和预防术后复发和转移有前途.

关键词:

在CD73封锁中.铁性化 (ferroptosis) 是一种免疫性细胞死亡免疫性细胞死亡金属-有机协调聚合物氧化风暴是一种氧化风暴.

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