通过类似病毒的颗粒对亚洲糖蛋白受体进行多价值向
Robert Hincapie1, Sonia Bhattacharya1, Michael M Baksh1
1School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA, 30332, USA.
Small (Weinheim an der Bergstrasse, Germany)
|August 31, 2023
概括
针对亚亚糖蛋白受体 (ASGPR) 的病毒样颗粒 (VLP) 显示出肝脏的有效吸收. 然而,由于其他肝细胞的吸收,实现选择性肝细胞输送仍然具有挑战性.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 纳米医学是一种纳米医学.
- 细胞生物学 细胞生物学
背景情况:
- 亚亚糖蛋白受体 (ASGPR) 在肝细胞上高度表达,为肝脏特异性药物输送提供了点.
- 多价银河系糖化碳水化合物与ASGPR结合,促进肝脏输送结合分子.
研究的目的:
- 开发和评估病毒样粒子 (VLP) 结合物,以实现高效的ASGPR介导的肝输送.
- 为了研究连接体密度和亲缘关系对VLP细胞吸收和肝脏向的影响.
主要方法:
- 结合高亲和力银河系结合联体到VLPs.
- 通过ASGPR表达的HepG2细胞对VLP内细胞的体外评估.
- 针对性和非针对性VLP在小鼠中的体内生物分布研究.
主要成果:
- 优化的VLP-连接体结合体显示出高效的ASGPR-依赖性内细胞分解,优于小分子和自然连接体.
- 活体研究显示,肝脏清除速度快,并与各种肝细胞类型的关联,包括肝细胞,库普弗细胞和鼻状内皮细胞.
- 虽然ASGPR向的VLP与非向的VLP相比,显示肝细胞协会增加,但非基细胞的显著吸收限制了选择性向.
结论:
- 针对ASGPR的VLP代表了肝脏输送的有希望的平台,吸收效率取决于连接体特征.
- 尽管具有强大的ASGPR向性,但由于库普弗细胞和内皮细胞的大量吸收,实现独家肝细胞输送是具有挑战性的.
- 肝脏内的选择性细胞贩运仍然是一个重大障碍,即使有优化的准策略.
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