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理性设计的多功能纳米颗粒作为基于来自德克斯和β-环氧德克斯林的宿主-客聚合物的GSH响应性抗癌药物输送系统

Xichuan Tang¹, Yuting Wen¹, Zhongxing Zhang²

¹Department of Biomedical Engineering, National University of Singapore, 15 Kent Ridge Crescent, Singapore 119276, Singapore.

Carbohydrate polymers

|September 2, 2023

概括

这项研究开发了新型纳米颗粒,用于同时在癌细胞中输送胺 (LND) 和谷氨酸 (GSH) 耗尽. 这种方法增强了LND的优势.

科学领域:

生物医学工程生物医学工程
纳米技术纳米技术
癌症研究癌症研究

背景情况:

线粒体的能量生产推动了瘤的生长和转移.
隆尼达胺 (LND) 抑制了线粒体六金酶,显示出作为抗癌药物的潜力.
由于LND的水溶性有限,以及癌细胞中的谷氨 (GSH) 含量限制了它的有效性.

研究的目的:

开发一种系统,同时在癌细胞中传递LND和减少GSH.
创建一种方法来监测癌细胞内的GSH水平.
通过一种新的纳米粒子系统来增强LND的抗癌疗效.

主要方法:

主体聚合物β-cyclodextrin-polyethylenimine (β-CD-PEI) 和客体聚合物德克斯-5-dithio-(2-nitrobenzoic acid) (Dextran-SS-TNB) 的合成.
通过宿主-客人复合形成LND载荷,GSH响应的纳米粒子.
在实验室中对纳米粒子介导的GSH耗尽,ROS升高和线粒体功能障碍和免疫细胞死亡 (ICD) 的诱导进行评估.

主要成果:

开发的纳米粒子成功地提供了LND和耗尽的细胞内GSH.
由于GSH的减少,反应性氧物种 (ROS) 水平增加.
该系统诱导了基于LND的线粒体功能障碍和ROS介导的ICD,从而产生了协同作用的抗癌效应.
释放的TNB2-作为410nm可见光吸收的探针,用于监测GSH水平.

结论:

装载着LND,对GSH有反应的纳米粒子为癌症治疗提供了一个有前途的策略.
同时提供LND和耗尽GSH可以提高抗癌效果.
该系统提供了一种用于实时监测癌细胞GSH水平的新方法.

关键词:

5,5′-Dithiobis-(2-nitrobenzoic 酸) 的使用情况.德克斯兰 (Dextran) 是一种葡萄糖氨酸 (Glutathione) 是一种免疫细胞死亡免疫细胞死亡隆尼达胺是一种胺.这是β-Cyclodextrin.

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