去唾液酸糖蛋白受体及其在药物肝靶向递送中的应用

Asialoglycoprotein Receptor and Its Application in Liver-targeted Drug Delivery

去唾液酸糖蛋白受体(ASGPR)是肝细胞特异性表达的受体,且是一种高效的内吞型受体,去唾液酸糖蛋白、半乳糖、半乳糖胺、N-乙酰半乳糖胺等糖分子对其有高亲和性.该综述回顾了ASGPR的发现历程、结构特征、生物学功能、表达模式、胞吞特点.总结了影响ASGPR与其配体亲和、介导胞吞的影响因素(包括配体类型、触角数量、空间距离与颗粒粒径).概述了早期ASGPR与其特异性配体在药物递送中的应用.最后介绍了最近利用N-乙酰半乳糖胺的缀合或修饰来实现肝靶向核酸药物递送的研究进展.

Asialoglycoprotein receptor （ASGPR） was specifically expressed by hepatocytes, which could recognize and bind asialoglycoprotein, galactose （Gal）, galactosamine, N-acetylgalactosamine （GalNAc）, etc. with high affinity. In a receptor-mediated-endocytosis （RME） manner, various molecules could be delivered into hepatocytes effectively. In this review, we firstly introduced the discovery, structure, function, expression pattern and endocytosis properties of ASGPR. Then the influence factors of ligand/receptor interaction and RME, including ligand species, valence, orientation and particle size, were analyzed. In addition, studies on ASGPR-mediated drug delivery in the past decades were reviewed. More importantly, progress in GalNAc-conjugation or -modification technologies employed in liver-targeted transportation of siRNA, antisense and antagomir were summarized.