通过使用反向电子需求的迪尔斯-阿尔德化学和基于ectoenzyme的连接体激活来实现可切换的纳米粒子行为
Johannes Lang1, Kathrin Schorr1, Achim Goepferich1
1Department of Pharmaceutical Technology, University of Regensburg, Regensburg, 93053, Germany.
概括
响应刺激的纳米粒子 (NP) 可以使用化学触发器来切换受体相互作用. 这项研究开发了一种由NP进行向细胞识别的两步过程,提高了药物输送的特异性.
科学领域:
- 生物医学工程 生物医学工程
- 纳米技术 纳米技术
- 药物输送系统 药物输送系统
背景情况:
- 纳米粒子 (NP) 在药物输送中面临生物和物理障碍.
- 响应刺激的NP提供适应性特性来克服这些挑战.
- 有针对性的交付需要精确控制NP与生物系统的相互作用.
研究的目的:
- 通过外部化学刺激开发可调节的纳米粒子 (NP),具有可调节的受体相互作用.
- 设计一个两步目标细胞识别系统,以提高药物输送的特异性.
- 为了利用反向电子需求的Diels-Alder (iEDDA) 化学和ectoenzyme激活来进行连接物定制.
主要方法:
- 使用iEDDA点击化学,用一个不活跃的 ангиотензин-I (Ang-I) 配体对NP进行功能化.
- 通过在目标部位的细胞外酶,酶激活Ang-I转化为 ангиотензин-II (Ang-II).
- 通过Ang-II与胰腺激素II型1 (AT1) 受体结合来识别细胞.
主要成果:
- 由化学刺激触发的受体与可切换NP相互作用的证明.
- 成功实施了两步识别过程,包括酶联体激活.
- 通过受控的酶处理和受体结合,实现了增强的NP目标细胞特异性.
结论:
- 这种方法使特定的粒子适应能够克服药物输送中的生物障碍.
- 开发的方法通过延迟连接体激活来最大限度地减少非目标生物效应.
- 具有酶激活的刺激反应性NP代表了针对性治疗的有前途的战略.
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