双块共聚物的合理设计使得有效的细胞质蛋白递送成为可能
Hongyang Zhao1, Chenglin Zhang2, Chang Tian1
1State-Key Laboratory of Chemical Engineering, and Shanghai Key Laboratory of Multiphase Materials Chemical Engineering, East China University of Science and Technology, 130 Meilong Road, 200237 Shanghai, People's Republic of China.
Journal of colloid and interface science
|June 20, 2024
概括
研究人员开发了一种新型的双阻塞共聚合物,用于有效的细胞质蛋白质输送. 这种聚合物形成纳米粒子,使各种蛋白质的输送和抑制瘤生长 in vivo.
科学领域:
- 生物材料科学 生物材料科学
- 纳米技术纳米技术
- 药物运输 药物运输 药物运输
背景情况:
- 聚合物介导的蛋白质输送是蛋白质治疗的有希望的策略.
- 对许多基于蛋白质的疗法来说,有效的细胞质递送仍然是一个挑战.
- 现有的输送系统经常在蛋白质结合,内体体逃逸和向输送方面扎.
研究的目的:
- 设计和合成一种新型的双块共聚合物,以有效地在体外和体内输送细胞质蛋白质.
- 为了研究共聚合物结合蛋白质的能力,促进内体逃生,并触发细胞内释放.
- 评估共聚合物的向传递和治疗应用的潜力.
主要方法:
- 设计和合成一个双块共聚合物与一个蛋白质结合/内体逃生块 (PBA/DMAP) 和一个PEG块.
- 优化共聚物组成,序列和长度,以确定最佳变体 (BP20).
- 实验室纳米粒子形成,蛋白质负载,细胞质递送评估 (酶,有毒蛋白质,RNP) 和细胞系研究.
- 使用叶酸 (FA) 修饰的PEG阻断剂和Saporin进行体内瘤向输送研究,评估瘤生长抑制.
主要成果:
- 优化的双块共聚合物 (BP20) 有效地形成了各种蛋白质的稳定纳米粒子.
- 在BP20中介作用下,酶,有毒蛋白和CRISPR/Cas9核糖蛋白 (RNP) 的有效细胞溶液传递到多个细胞系.
- 经过FA修改的BP20在体内证明了瘤向的输送,通过Saporin输送显著抑制了瘤生长.
结论:
- 设计的双块共聚合物代表了一个强大的平台,用于细胞质蛋白质的输送.
- 这种新型的聚合物载体显示出生物研究工具和治疗应用的巨大潜力.
- 这项研究为设计用于细胞内蛋白质输送的先进聚合物系统提供了蓝图.
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