蛋白冠形成机理及其在纳米载体设计中的应用进展  

Mechanism of Protein Corona Formation and Its Application Progress in Nanocarrier Design

作　　者：李卓婷 吴宏辉 张添源 高建青[1,2] LI Zhuoting;WU Honghui;ZHANG Tianyuan;GAO Jianqing(College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China;Jinhua Research Institute,Zhejiang University,Jinhua 321015,China)

机构地区：[1]浙江大学药学院,杭州310058 [2]浙江大学金华研究院,浙江金华321015

出　　处：《中国现代应用药学》2024年第20期2806-2815,共10页Chinese Journal of Modern Applied Pharmacy

基　　金：国家自然科学基金联合基金重点项目(U22A20383);浙江省自然科学基金重大项目(LD22H300002)。

摘　　要：纳米尺寸的靶向药物递送系统在药剂学领域获得极大关注。纳米粒在接触血液后,表面会迅速吸附多种类型的蛋白质,形成蛋白质包裹层,即蛋白冠。蛋白冠的存在会影响纳米粒的体内识别、分布和代谢过程,影响纳米粒的靶向递送效率。对于蛋白冠形成机理的深入解析可为纳米粒的设计及其应用提供依据。利用蛋白冠-纳米粒之间相互关系,主动调控蛋白冠以提高纳米载体的递送效率逐渐成为研究热点。基于此,本文对蛋白冠的形成原理和影响因素进行综述,分析蛋白冠对纳米载体体内循环、靶向能力和免疫识别的影响及其应用,最后提出目前蛋白冠及其应用存在的主要挑战和未来前景。Nanoscale targeted delivery systems have gained increasing attention in the field of drug delivery due to their unique physicochemical properties and potential clinical applications.However,once these nanoparticles were systemically administrated,they rapidly adsorb a variety of proteins from the plasma on the surface,forming a complex protein layer known as the"protein corona".The formation of the protein corona is a dynamic and multi-step process.It involves the selective adsorption and desorption of multiple plasma proteins.This process adheres to the"Vroman effect".In such systems,proteins of higher concentration initially binding to the material surface but eventually being replaced by those with higher affinity.Protein adsorption on the nanoparticle surface results in the formation of two layers:inner layer as"hard corona"and outer layer as"soft corona".Proteins in the hard corona bind directly to the nanoparticle surface with high affinity.They form a stable,non-exchangeable layer that confers new biological properties to the nanoparticles.The soft corona consists of proteins that indirectly associate with the nanoparticle surface.These associations occur through interactions with components of the hard corona.The soft corona forms a highly exchangeable layer,dependent on the type of biological fluid.The composition and structure of the protein corona are impacted by nanoparticle properties,including size,shape,surface charge,and surface chemistry.In vivo environmental factors also impact the corona,such as blood protein concentrations,contact time with proteins and disease microenvironments.The presence of the protein corona significantly alters the biorecognition characteristics of nanoparticles,thereby impacting their in vivo fate,including circulation time,organ and tissue distribution,eventual metabolism and excretion processes.These changes significantly affect the targeting efficiency of nanoparticles as therapeutic agent carriers.Given the critical role of the protein corona in determining the in v

关 键 词：药物靶向递送 蛋白冠 纳米载体 纳米-生物相互作用 

分 类 号：R945[医药卫生—微生物与生化药学]