药学学报, 2022, 57(1): 64-75
引用本文:
嵇梦, 陈大力, 涂家生*, 孙春萌*. 基于组氨酸的肿瘤靶向药物递送系统研究进展[J]. 药学学报, 2022, 57(1): 64-75.
JI Meng, CHEN Da-li, TU Jia-sheng*, SUN Chun-meng*. Research progress of histidine-based tumor-targeting drug delivery systems[J]. Acta Pharmaceutica Sinica, 2022, 57(1): 64-75.

基于组氨酸的肿瘤靶向药物递送系统研究进展
嵇梦, 陈大力, 涂家生*, 孙春萌*
中国药科大学, 药用辅料及仿创药物研发评价中心, 药学院, 国家药品监督管理局药物制剂及辅料研究与评价重点实验室, 江苏 南京 210009
摘要:
组氨酸作为一种碱性氨基酸,pKa接近肿瘤弱酸微环境pH,其带电性和溶解性具有pH敏感性,在中性环境中,组氨酸不带电,表现为疏水特性,而在肿瘤酸性环境中,组氨酸可质子化带正电,同时转变为亲水特性,因此,组氨酸被广泛应用于靶向肿瘤弱酸性微环境的药物递送系统设计。本文全面综述了近年来基于组氨酸构建肿瘤靶向药物递送系统的研究进展,系统总结了利用组氨酸促进细胞摄取和调控药物释放的设计思路,并指出了相关研究工作的共性问题和未来发展方向。
关键词:    组氨酸      细胞穿膜肽      肿瘤微环境      药物递送系统      药物治疗     
Research progress of histidine-based tumor-targeting drug delivery systems
JI Meng, CHEN Da-li, TU Jia-sheng*, SUN Chun-meng*
NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, Center for Research Development and Evaluation of Pharmaceutical Excipients and Generic Drugs, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
Abstract:
As a basic amino acid, histidine has a pKa close to the acidity of the tumor microenvironment, thus the charge and solubility of histidine are able to vary as the pH changes. Under a neutral environment, histidine is not charged and exhibits hydrophobic properties, while it can be protonated and becomes hydrophilic when exposed to mildly acidic pH, such as tumor microenvironment. Therefore, histidine is widely used in the design of drug delivery systems to target the mildly acidic pH of tumor microenvironment. This article reviews the recent progresses of histidine-based tumor-targeting drug delivery systems, and summarizes the principles on promoting internalization and tuning drug release by taking advantage of histidine. Finally, we point out the common issues on histidine application and illustrate its future prospects.
Key words:    histidine    cell-penetrating peptide    tumor microenvironment    drug delivery system    therapy   
收稿日期: 2021-08-11
DOI: 10.16438/j.0513-4870.2021-1174
基金项目: 国家自然科学基金资助项目(81972894,81673364)
通讯作者: 涂家生,Tel:86-25-83271305,E-mail:jiashengtu@cpu.edu.cn;孙春萌,E-mail:suncmpharm@cpu.edu.cn
Email: jiashengtu@cpu.edu.cn;suncmpharm@cpu.edu.cn
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