基于酸的可降解纳米凝:模块化纳米载体,用于安全,全身的托尔类受体7/8激动性免疫调节剂
Anne Huppertsberg1, Leonard Kaps2,3, Zifu Zhong4
1Max Planck Institute for Polymer Research, 55128 Mainz, Germany.
Journal of the American Chemical Society
|June 24, 2021
概括
新的纳米凝可以安全地提供Toll-like受体7/8激活剂用于癌症治疗和疫苗接种. 这些对pH敏感的纳米载体可以预防全身炎症,通过静脉注射进行向免疫刺激.
科学领域:
- 生物技术
- 纳米医学
- 免疫学
背景情况:
- 托尔类受体7/8 (TLR7/8) 激动剂是用于癌症治疗和疫苗接种的强有力的免疫调节剂.
- 小分子TLR7/8激动剂的全身使用导致非向性炎症效应,限制了它们的临床应用.
- 开发TLR7/8激动剂的安全有效的输送系统对于免疫治疗至关重要.
研究的目的:
- 设计和制造适应pH的纳米凝,用于安全的静脉输送TLR7/8刺激的伊米达佐基诺林.
- 创建一个纳米载体系统, 实现受控释放和向免疫激活.
- 评估纳米凝与药物合物的免疫调节效果和安全性.
主要方法:
- 通过RAFT聚合合成PEG衍生的二胺块共聚物.
- 聚合物的自我组装成氨基反应前体,并随后通过 imidazoquinolines 进行功能化.
- 纳米凝性质的表征,包括人体血中的pH反应降解和稳定性.
- 在体内评估巨细胞的免疫调节活性,在体内评估生物分布和炎症反应.
主要成果:
- 能够封装TLR7/8激动剂 (imidazoquinolines) 的稳定,响应pH的纳米凝.
- 在内溶体pH条件下显示纳米凝的刺激反应降解.
- 在实验室中,纳米凝结合的伊米达佐基诺林具有免疫调节作用.
- 在体内*, 纳米凝的静脉注射导致了在脏中空间控制的免疫刺激活性,而没有系统的异位炎症.
结论:
- 基于酸的,可降解的纳米凝是安全的小分子TLR7/8激动剂静脉输送的有希望的平台.
- 这种纳米载体系统减轻了全身毒性,使得有针对性的免疫刺激成为可能.
- 开发的纳米凝在全身疫苗接种和癌症免疫治疗中具有增强辅助疗效的潜力.
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