多功能点击链接器,在Redox触发时从纳米载体释放原生
Erik R Hebels1, Stefanie Dietl1, Matt Timmers1,2
1Division of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht 3508 TB, The Netherlands.
Bioconjugate chemistry
|December 11, 2023
概括
我们开发了一种新的链接器,用于将治疗性附在纳米载体上,从而实现有效的药物输送和释放. 这种方法改善了类药物递送,并增强了瘤细胞的杀死.
科学领域:
- 生物结合化学 生物结合化学
- 纳米医学是一种纳米医学.
- 药物输送系统 药物输送系统
背景情况:
- 纳米载体增强药物循环,瘤吸收和释放动力学.
- 治疗性受益于改进的输送策略,以提高其治疗指数.
- 坐标共价连接器化学对于合成,纳米载体结合和触发释放至关重要.
研究的目的:
- 开发一种用于将治疗性酸与纳米载体结合的新型链接器.
- 为了促进在树脂上的生成,纳米载体结合,并触发本地的释放.
- 为了研究一种新的链接-联系统在癌症治疗中的有效性.
主要方法:
- 固相合成 (SPPS) 用于将一个无铜可点击链接器 (TMTHSI) 与解性体LTX-315结合.
- 通过点击化学,将链接联物附加到含有亚酸的基化核心交联聚合物微粒 (CCPM) 上.
- 使用谷氨的体外释放研究和对1,6-消除的分析.
- 使用细胞培养的细胞毒性和细胞吸收研究.
主要成果:
- 合成了一种新型链接剂,其中含有压缩的基因,二硫化键和乙烯基碳酸盐间隔剂,并与LTX-315结合.
- 在水性条件下,水友性链接联体在50纳米的CCPM上有效地加载 (8质量%的负载,56%的效率).
- 试验室研究表明,在暴露于谷氨时,LTX-315的快速释放,随后是1,6-消除,产生原生.
- LTX-CCPMs对瘤细胞表现出强烈的细胞毒性,相当于自由的LTX-315.
结论:
- 一个新的,直角链接系统使治疗性酸能够高效地与纳米载体结合.
- 开发的纳米载体系统有效地提供和释放治疗性,增强抗癌活性.
- 这种方法为改善基于的药物的治疗指数提供了一个有希望的策略.
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