粘合剂光启动器在酶上构建聚合物克:直接,无释放的细胞质递送
Shuran He1, Soumen Ghosh1,2, Kou Okuro1,2
1Department of Chemistry, The University of Hong Kong, Hong Kong, SAR, P.R. China.
Angewandte Chemie (International ed. in English)
|January 30, 2026
概括
我们开发了一种新型的超分子系统,以保护酶用于治疗. 该系统增强了酶的稳定性,并确保了有效的输入细胞,克服了当前酶疗法的关键挑战.
科学领域:
- 生物材料科学 生物材料科学
- 纳米技术 纳米技术
- 酵素工程是什么? 酶工程是什么
背景情况:
- 酶疗法在维持催化活性和实现高效的细胞质递送方面面临着挑战.
- 目前的保护性封装方法往往会损害酶功能和细胞吸收.
- lysosomal 降解是传递到细胞的治疗酶的一个重要障碍.
研究的目的:
- 开发一种用于酶保护和输送的新型超分子系统.
- 创建一个系统,统一表面粘附,激素启动和膜转移.
- 为了使酶在保持其催化活性的同时能够有效地通过细胞溶液传递酶.
主要方法:
- 一个超分子粘光启动器 (GuCDBP-SH) 的设计,使用瓜尼尼 (Gu+) 图案和一个环德克斯特林支架 (GuCD).
- 宿主-客人复杂化在循环德克斯特林腔内的醇-二客人 (BP-SH).
- 光激活以启动从聚合物接种,在酶周围形成半透的聚合物外套.
- 适用于beta-galactosidase,形成100nm以下的纳米组件.
主要成果:
- 纳米组件保留了大约30%的催化活性,在蛋白酶K挑战后保留了86%的活性.
- 与未受保护的酶相比,证明了异常的蛋白质溶解耐药性 (25%的活性保留).
- 通过膜转位实现了高效,能源独立的细胞质递送,91%的细胞表现出活性.
结论:
- 模块化策略成功地赋予了对本地生物大分子的保护和细胞透能力.
- 在不影响酶递送效率的情况下保持催化功能.
- 消除了对酶释放的需求,解决了治疗交付中持续存在的瓶.
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