药学学报, 2021, 56(2): 476-486
引用本文:
赵耀, 杨璨羽, 张强, 王学清. 肿瘤氧化还原微环境响应型小分子前药纳米粒的代谢与药效研究进展[J]. 药学学报, 2021, 56(2): 476-486.
ZHAO Yao, YANG Can-yu, ZHANG Qiang, WANG Xue-qing. Research progress on metabolism and efficacy of small molecular prodrug nanosystems responsive to tumor redox microenvironment[J]. Acta Pharmaceutica Sinica, 2021, 56(2): 476-486.

肿瘤氧化还原微环境响应型小分子前药纳米粒的代谢与药效研究进展
赵耀, 杨璨羽, 张强, 王学清
北京大学药学院, 北京 100191
摘要:
与正常组织、细胞的微环境相比,肿瘤微环境具有显著差异,如谷胱甘肽相关代谢酶和活性氧在不同亚细胞结构中高表达,造成氧化还原状态失衡。根据这种特异性的氧化还原状态,可以设计一系列通过氧化还原响应型连接臂相连的小分子前药纳米粒。常见的连接臂有二硫键、硫醚键、硒键和硫缩酮键等。不同连接臂的小分子前药纳米粒具有不同的代谢方式和体内外药效作用。本篇综述将从肿瘤细胞特异性氧化还原状态、智能响应型小分子前药纳米粒的设计、不同连接臂的小分子前药纳米粒的代谢方式及其与药效的关系等方面来总结肿瘤氧化还原微环境响应型小分子前药纳米系统的研究进展。
关键词:    氧化还原响应      小分子前药纳米粒      二硫键      硫醚键      细胞药代动力学      抗肿瘤药效     
Research progress on metabolism and efficacy of small molecular prodrug nanosystems responsive to tumor redox microenvironment
ZHAO Yao, YANG Can-yu, ZHANG Qiang, WANG Xue-qing
School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
Abstract:
Compared with normal tissues and cells, the tumor microenvironment has significant differences. For example, glutathione-related metabolic enzymes and reactive oxygen species are highly expressed in different subcellular structures, resulting in an unbalanced redox state. Aiming at the specific redox state in tumor tissues and cells, a series of small molecule prodrug self-assembled nanoparticles can be designed and connected by intelligent response linkers including disulfide bonds, sulfide bonds, and selenium bonds, thioketal bonds, etc. The in vitro and in vivo efficiency and metabolic mode of these nanoparticles are related to the type of linker. This review will summarize the tumor redox microenvironment, the design of intelligent responsive small molecule prodrug nanoparticles, and the metabolic pathways of small molecule prodrug nanoparticles with different connecting linkers and their relationship with drug efficacy.
Key words:    oxidation-reduction responsive    small-molecule prodrug nanoparticle    disulfide bond    thioether bond    cellular pharmacokinetics    antitumor effect   
收稿日期: 2020-07-23
DOI: 10.16438/j.0513-4870.2020-1234
基金项目: 国家自然科学基金资助项目(31671017,81872809,82073786).
通讯作者: 王学清,Tel/Fax:86-10-82805935,E-mail:wangxq@bjmu.edu.cn
Email: wangxq@bjmu.edu.cn
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