通过工程化区块共聚物两聚物-TLR7/8激动剂的淋巴结向免疫激活
Simon Van Herck1, Kim Deswarte2,3, Lutz Nuhn1
1Department of Pharmaceutics and Cancer Research Institute Ghent (CRIG) , Ghent University , Ghent 9000 , Belgium.
Journal of the American Chemical Society
|October 3, 2018
概括
小分子免疫调节剂结合阻断共聚物以增强淋巴输送,提高疗效和减少副作用. 这种策略将药物的作用局限于淋巴组织,优化先天免疫反应.
科学领域:
- 免疫学
- 聚合物化学
- 提供药物
背景情况:
- 小分子免疫调节剂,如托尔类受体 (TLR) 激动剂,刺激先天免疫细胞产生抗病毒和抗瘤作用.
- 这些小分子的全身循环导致"浪费炎症"和毒性.
- 针对淋巴组织的药物作用对于提高疗效和尽量减少副作用至关重要.
研究的目的:
- 开发一种合成策略,将小分子免疫调节剂限制在淋巴组织中.
- 改善TLR7/ 8激动剂的药理学特征,以增强淋巴输送.
- 制造一种能够应对酸性内体环境的药物输送系统.
主要方法:
- 一个小分子TLR7/8激动剂与形成菌的两块共聚物的共价结合.
- 采用 π-π 叠加的块共聚物的设计,以获得菌稳定性.
- 工程块共聚物用于适应pH的两性到水性过渡.
主要成果:
- 结合的TLR7/8激动剂表现出改变的药理学特征,实现了高效的淋巴输送.
- 通过区块共聚物中的芳香部分之间的 π-π 堆叠形成了热力学稳定的小粒.
- 工程化块共聚物在对酸性内体pH的反应中表现出一种不可逆转的从两性转变为水性转变.
结论:
- 将小分子免疫调节剂与两性阻断共聚物结合是向淋巴输送的有效策略.
- 通过将其集中在淋巴组织中,开发的细胞系统提高了药物的有效性.
- 微粒的pH反应性提供了在内体内控制药物释放的潜力,优化了免疫调节反应.
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