可聚合的二三甲基化物作为适应pH的免疫药物的宏分子载体平台
Alina G Heck1, Judith Stickdorn1, Laura J Rosenberger2
1Max Planck Institute for Polymer Research, Mainz 55128, Germany.
Journal of the American Chemical Society
|December 6, 2023
概括
研究人员开发出新型聚合物, 药物在酸性pH条件下释放出来, 理想用于向免疫治疗. 与初级氨基相比,二次氨基结合表明药物活性和免疫细胞成熟度有所提高.
科学领域:
- 聚合物化学
- 生物材料科学
- 药物输送系统
背景情况:
- 具有刺激反应的聚合物为克服药物输送中的生物障碍提供了先进的解决方案.
- 特别是在细胞吸收后,pH触发的释放机制对向的治疗提供特别有希望.
- 开发能够结合药物并在特定的pH条件下释放的聚合物对于有效的治疗至关重要.
研究的目的:
- 设计和合成能够结合初级或二级氨基的新型甲胺基聚合物.
- 从这些聚合物中研究pH触发的药物释放,重点关注与内体环境相关的酸性条件.
- 评估这些聚合物药物合物的免疫治疗效果,比较初级和二级氨基修饰的性能.
主要方法:
- 基于甲基胺的单体与悬挂二三甲基化基的合成.
- 使用可逆添加碎片链转移 (RAFT) 聚合这些单体.
- 氨基反应性无水化物与初级和二级氨基的衍生,以形成性聚合物.
- 在体外评估pH触发的药物释放,聚合物毒性,细胞吸收和免疫细胞反应.
主要成果:
- 聚合物成功结合了初级和二级氨基,形成了水友性结构.
- 在酸性条件下,二次胺结合导致了数量上由pH触发的药物释放,与初级胺形成的不可逆转的胺结合不同.
- 在体外研究中没有显著的聚合物毒性和高细胞吸收.
- 与初级氨基衍生物相比,二次氨基修饰免疫刺激药物表现出更高的受体活性和免疫细胞成熟.
结论:
- 基于2-propionic-3-methylmaleic无水化物的聚合物代表了pH触发免疫治疗药物的多功能平台.
- 基于氨基类型 (主要与次要) 的差异释放机制允许微调药物输送和治疗效果.
- 这种方法对推进宏分子辅助免疫疗法具有重大潜力.
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