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在缺血性中风中潜在的治疗性低温的pH/温度双响应蛋白质-聚合物结合物

Lingli Jin^1,2, Fengjiao Chen^1,2, Xianwu Chen³

¹Center for Child Care and Mental Health, Shenzhen Children's Hospital Affiliated to Shantou University Medical College, Shenzhen 518026, China.

ACS applied bio materials

|October 31, 2023

概括

这项研究引入了一种用于治疗缺血性中风的新型双反应合物 (PEG-uPA-PEG-PPG-PEG). 它在轻度低温下增强血栓溶解,同时在正常热量下降出血风险.

科学领域:

生物材料科学生物材料科学
神经科学是一个神经科学.
药理学药理学是指药理学的学科.

背景情况:

缺血性中风的血栓溶解疗法面临限制,包括狭窄的治疗窗口和不良影响.
治疗性低温显示出对中风的神经保护潜力,但需要优化药物输送系统.
现有的治疗方法需要提高安全性和疗效,特别是对于出血并发症.

研究的目的:

开发新的pH/温度双响应蛋白质聚合物结合物,用于增强缺血性中风血栓溶解.
创建一个系统,在生理条件下掩盖尿素酶类型等离子体激活剂 (uPA) 的生物活性,并在低温,酸性条件下恢复它.
研究这种结合物的潜力,以减少出血并发症,同时提高缺血性中风的治疗疗效.

主要方法:

用聚乙烯糖醇 (PEG) 和热敏聚合物 (PEG-PPG-PEG) 修改尿素酶类型的塑原激活剂 (uPA),使用pH敏感的胺和二硫化键.
在不同温度和pH条件下 (37°C/pH 7.4对33°C/pH 6.0) 进行双反应合物 (PEG-uPA-PEG-PPG-PEG) 的表征.
对uPA生物活性恢复和PEG/PEG-PPG-PEG行为转移的评估,以应对模拟的生理和中风部位微环境.

主要成果:

在常温 (37°C) 和生理pH (7.4) 时,由于聚合物屏蔽,结合物表现出掩盖的uPA生物活性,减少了抗蛋白酶水解.
在轻度低温 (33°C) 和酸性pH (6.0) 条件下,PEG解离和聚合物拉伸发生,恢复uPA生物活性.
双反应性质成功控制了uPA的释放和活性,证明了有针对性血栓溶解的潜力.

结论:

开发的PEG-uPA-PEG-PPG-PEG合物为缺血性中风治疗提供了一个有前途的策略,通过在轻度低温下实现向血栓溶解.
在正常热量下掩盖uPA生物活性,显著降低了与血栓解压治疗相关的急性出血并发症的风险.
这种创新的生物材料有可能在缺血性中风管理中推进治疗性低温症策略.

关键词:

响应pH的反应性蛋白聚合物结合物的蛋白聚合物一次性中风中风中风中风中风治疗性低温症治疗性低温症热响应性热反应性泌尿酸酶类型的塑原激活剂

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