蛋白质和聚合物的可逆组合用于细胞内蛋白质的输送,具有血清稳定性
Guangyu Rong1, Xujiao Zhou1, Jiaxu Hong1
1Department of Ophthalmology and Vision Science, Shanghai Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, 200030, China.
Nano letters
|April 15, 2024
概括
我们开发了一种新的纳米粒子系统,以细胞内输送蛋白质药物. 这种系统在血清中表现出很大的稳定性,并在细胞内有效释放药物,改善对视网膜氧化应激等疾病的治疗.
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:
- 蛋白质药物的细胞内输送受到低效率和血清稳定性差的阻碍.
- 现有的输送系统往往难以在生物环境中保护蛋白质疗法.
研究的目的:
- 开发一种强大而高效的基于纳米粒子的系统,用于细胞内蛋白质的药物输送.
- 提高血清稳定性和目标释放货物蛋白质.
主要方法:
- 使用可逆组装策略,采用异构功能适配器 (2-formylbenzeneboronic acid) 来连接货物蛋白和聚合物.
- 通过伊米诺酸盐和酸盐二链接形成纳米颗粒,确保稳定性和受控释放.
- 在培养基中评估纳米颗粒稳定性和由 lysosomal 酸度和谷氨 (GSH) 触发的货物释放.
主要成果:
- 在培养介质中为组装的纳米颗粒实现了出色的血清稳定性.
- 通过细胞内条件 (溶酶体酸度和GSH) 引发的快速货物蛋白释放被证明是内细胞化后的.
- 在动物模型中,通过静脉内注射,成功将超氧化物脱酶输送到视网膜.
- 显著改善氧化应激和细胞损伤在缺血-再输液 (I/R) 诱导的视网膜损伤与最小的不良影响.
结论:
- 可逆组装策略为生物宏分子的细胞内传递提供了稳定和有效的方法.
- 这种方法有望为各种疾病开发先进的治疗系统,特别是那些涉及氧化应激的疾病.
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