苯硼酸功能化聚合物纳米载体用于蛋白质药物胞内递送

Phenylboronic Acid Functionalized Polymer Nanocarriers for Intracellular Delivery of Protein Drugs

蛋白质药物在疾病治疗方面具有广泛应用,但它们的低细胞膜穿透性往往导致生物利用度较低.近年来,人们开发了一系列纳米载体用于提高蛋白质药物的胞内递送效率,其中基于苯硼酸及其衍生物的聚合物纳米载体显示出良好的应用前景.本文综述了苯硼酸功能化聚合物纳米载体在蛋白质药物胞内递送方面的最新研究进展.首先,简要介绍了苯硼酸的化学性质及其二醇、pH和活性氧(ROS)响应性.其次,从苯硼酸与蛋白质药物的结合方式不同出发,重点综述了通过动态共价作用和N→B配位等非共价作用构筑的苯硼酸功能化聚合物纳米载体在蛋白质药物胞内递送方面的典型研究实例,并对这些载体的组成、构筑方式和响应性释放机制进行了分析、总结.最后,介绍了利用苯硼酸增强细胞摄取和促进药物透过血脑屏障方面的研究进展.希望能为设计制备基于苯硼酸的新型蛋白质药物胞内递送体系提供借鉴.

Protein drugs have a wide range of applications in the treatment of many diseases.However,the poor cell membrane penetration of protein drugs often leads to low bioavailability.In recent years,a series of nanocarriers have been developed to improve the efficiency of intracellular delivery of protein drugs.Among them,nanocarrier based on phenylboronic acid and its derivatives have shown good application prospects.This paper reviews the latest research progress of phenylboronic acid-functionalized polymer nanocarriers for intracellular delivery of protein drugs.Firstly,the chemical properties of phenylboronic acid and its responsiveness to diols,pH and ROS are briefly introduced.Secondly,from the perspective of different binding modes of phenylboronic acid and protein drugs,this review focuses on the typical research examples of phenylboronic acid-functionalized polymer nanocarriers constructed by dynamic covalent bonds and non-covalent interactions such as N→B coordination in the intracellular delivery of protein drugs.The compositions,construction method,and responsive release mechanism of these nanocarriers are analyzed and summarized.Finally,the research progress of phenylboronic acid in enhancing cell uptake and drug permeation through blood brain barrier is introduced.It is hoped that this paper can provide a reference for the design and preparation of novel intracellular delivery systems of protein drugs based on phenylboronic acid.