基于去唾液酸糖蛋白受体的肝靶向药物的研究

The research of liver-targeted drugs based on asialoglycoprotein receptor

去唾液酸糖蛋白受体(asialoglycoprotein receptor,ASGPR)是一种在肝实质细胞表面高度表达的受体,它可以特异性识别和结合末端带有半乳糖或N-乙酰基半乳糖胺残基的分子,通过网格蛋白介导其内吞并转运至溶酶体中降解。基于这一特性,ASGPR介导的肝靶向药物递送会增加药物在肝脏中的分布、减少药物潜在不良反应并降低给药剂量。本文全面综述了ASGPR的表达、组成与结构、结合及内吞,系统总结了基于ASGPR的配体设计、优化及其释放策略,并展望该受体在药物开发中的应用。

Asialoglycoprotein receptor(ASGPR)is highly expressed on the surface of parenchymal liver cells.It can specifically recognize and bind to desialylated glycoproteins which contain terminal galactose or N-acetylgalactosamine residues,and endocytosed by clathrin-mediated endocytosis,transported and then degraded in lysosome.Based on this character,ASGPR mediated liver-targeted drug delivery is likely to increase drug distribution,reduce potential side effects and lower dose.This article reviewed the expression,structure,ligand binding and endocytosis of ASGPR,and summarized the design and optimization of ASGPR ligands and the release strategies.Finally,we put forward some expects about the clinical drug development for ASGPR.