蛋白质药物的胞质递送策略  

Strategies for Delivering Protein Drugs into the Cell Cytosol

作　　者：黄琳[1] 史永慧 吴军军 HUANG Lin;SHI Yonghui;WU Junjun(College of Life Sciences,Fujian Normal University,Fuzhou 350117,China)

机构地区：[1]福建师范大学生命科学学院,福州350117

出　　处：《中国细胞生物学学报》2025年第4期914-926,共13页Chinese Journal of Cell Biology

基　　金：福建省自然科学基金面上项目(批准号:2023J01506);福建省中青年教师教育科研项目(批准号:JAT220044);厦门大学翔安创新实验室/传染病疫苗研发全国重点实验室科技项目(批准号:2023XAKJ0101011)资助的课题。

摘　　要：蛋白质药物为糖尿病、癌症、心脑血管疾病等难以治愈的疾病带来了新的治疗希望,因为它们能特异性调节细胞内生化过程,且具有更高的生物相容性和安全性。但是大多数蛋白质药物分子量大且亲水性强,难以穿过细胞膜,仅能针对细胞外靶点,这一特性使可药化的靶点数目大打折扣。此外,蛋白质药物精细的三级结构和其特殊的生化性质极易受到外界因素的干扰而失去活性,这些固有局限严重制约了蛋白质药物在疾病治疗方面的应用。因此,开发理想的递送体系来弥补蛋白质药物的固有局限就变得尤其重要。各类能高效递送蛋白质进入胞质的定制修饰的递送体系被陆续开发出来,为蛋白质药物的研究与应用带来新的机遇。该文将介绍基于不同材料的蛋白质递送体系,如脂质递送系统、肽/蛋白质纳米递送系统、聚合物纳米递送系统和无机纳米递送系统在蛋白质药物胞质递送领域的发展近况。Protein drugs offer promising opportunities for treating complex diseases such as diabetes,can-cer,and cardiovascular disorders,owing to their ability to selectively modulate intracellular biochemical processes and their superior biocompatibility and safety.However,the clinical utility of most protein drugs is limited by poor cell membrane permeability,because of their large molecular size and high hydrophilicity.This limits their targeting to extracellular sites and reduces the range of druggable targets.Additionally,the complex tertiary struc-ture and unique biochemical properties of protein drugs make them highly vulnerable to external factors that can compromise their activity.These inherent limitations significantly constrain their application in disease treatment.Therefore,the development of efficient delivery systems to overcome these barriers is essential.Recently,several advanced delivery platforms capable of effectively transporting proteins into the cytoplasm have been developed,opening new avenues for both research and clinical applications.This review will introduce the recent develop-ments in protein delivery systems based on different materials,such as those based on liposomes,peptide/pro-tein nanocarriers,polymers,and inorganic,in the field of cytosolic delivery of protein drugs.

关 键 词：胞质递送 蛋白质药物 细胞穿膜肽 聚合物 脂质体 内体逃逸 膜融合 

分 类 号：R943[医药卫生—药剂学]