自助增强可编程释放多种治疗剂,通过可激活的异构体原药-酶组合,用于抗瘤治疗
Shanshan Jiang1,2, Bhaskar Gurram1,3, Junfei Zhu1
1Marshall Laboratory of Biomedical Engineering, International Cancer Center, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Laboratory of Evolutionary Theranostics, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518055, China.
一种新的前药组件 (NTP@GOx) 使用葡萄糖氧化酶 (GOx) 释放多种癌症药物. 该系统增强了瘤微环境 (TME) 中的药物释放,以改善抗瘤治疗.
科学领域:
- 生物医学工程 生物医学工程
- 材料科学 材料科学 材料科学
- 在瘤学瘤学.
背景情况:
- 具有内源刺激反应的前期药物提供有针对性的癌症治疗,毒性降低.
- 单独的活性氧物种 (ROS) 不足以在瘤微环境 (TME) 中完全释放药物.
研究的目的:
- 开发一种自我增强的,由酶组装的前药物系统,用于可编程释放多种治疗剂.
- 通过克服ROS触发释放的局限性来提高抗瘤治疗中的药物输送和疗效.
主要方法:
- 设计了一种异构体前药物 (NBS-TK-PTX,NTP),结合了对ROS敏感的硫基甲基 (TK) 链接剂,并与葡萄糖氧化酶 (GOx) 结合.
- NTP@GOx组件是为抑制的GOx活性设计的,在酸性TME中部分解离后恢复.
- GOx催化过氧化生成触发了TK链接器裂变和药物释放,以及进一步的组装解离.
主要成果:
- 在NTP@GOx会议上,在应对TME条件时,展示了一种自我提升的多步释放机制.
- GOx活性最初被NTP抑制,随后在TME中恢复和放大.
- 该系统成功释放了用于化疗的帕克利塔塞尔 (PTX) 和用于光动力学治疗的NBS.
结论:
- 开发的ROS可激活的异构体前药组件 (NTP@GOx) 能够实现可编程的,自我促进的多种抗癌药物的释放.
- 这种方法通过提高药物输送和疗效,显示出多模式协同癌症治疗的巨大潜力.
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