核定位信号肽修饰的抗肿瘤纳米载药体系  

The Anti-tumor Nano-drug Carrier System Modified by the Nuclear Localization Signal Peptide

作　　者：李若瑾 吴晓雪 王澈[1,2] LI Ruo-Jin;WU Xiao-Xue;WANG Che(College of Chemistry and Chemical Engineering,Liaoning Normal University,Dalian 116029,Liaoning,China;Liaoning Key Laboratory of Biotechnology and Molecular Drug Development,Dalian 116081,Liaoning,China)

机构地区：[1]辽宁师范大学化学化工学院,辽宁大连116029 [2]辽宁省生物技术与分子药物研发重点实验室,辽宁大连116081

出　　处：《中国生物化学与分子生物学报》2022年第1期35-41,共7页Chinese Journal of Biochemistry and Molecular Biology

基　　金：辽宁省自然科学基金指导计划项目(No.2019-ZD-0467);辽宁省教育厅重点室平台项目(No.L201683653)资助。

摘　　要：纳米载药体系作为一类具有可控性和靶向性的药物递送工具,可以保护生物分子药物免于细胞内快速酶促降解、免于快速血液清除,确保将生物分子药物安全递送至作用部位,从而有效改善药物的生物利用度,提高药物疗效并降低毒副作用,在生物医学领域具有广阔的应用前景,在功能材料研究和肿瘤靶向治疗研究中受到广泛关注。近年来,通过使用功能性生物分子对纳米载药体系表面进行功能化修饰,进一步改善其生物相容性和药物的生物活性是纳米医学研究的热点。细胞核是很多抗肿瘤物质的主要作用位点,而核定位信号(nuclear localization signal,NLS)肽,作为一类能够识别并定位于细胞核的功能化多肽,能够穿透生物膜并靶向细胞核,被认为是构建纳米载药体系的通用工具。将核定位信号肽用于构建具有核靶向能力的功能化纳米载药体系,在抗肿瘤治疗领域具有重要的应用价值。尽管目前已经开发出多种核靶向功能化纳米载药体系的合成工艺,但是由于制备成本高和合成工艺复杂,将核靶向纳米载体从实验阶段转化到临床阶段还有一段漫长的研究过程。本文重点从核靶向功能化纳米载药体系的组成与构建入手进行阐述,对其入核方式和入核条件进行分析,并针对抗肿瘤纳米载药体系现存的问题对今后发展的方向作出展望。Nano-drug carrier systems,as the controllable and targeting tool to deliver drugs,can effectively improve the drug bioavailability,enhance their therapeutic outcomes and reduce side effects,mainly through protecting drugs from rapid enzymatic degradation and blood clearance and ensuring them to be delivered to the targeting sites.The nano-drug carrier system owns broad application prospects in the biomedical field and attracts increasing attention in both functional materials and anti-tumor research.Recently,functional surface modification with functional biomolecules to improve the biocompatibility and drug bioactivity is a hot topic in nano medicine research.The nucleus is the main site of action for many anti-tumor substances.And nuclear localization signal(NLS)peptides,as a type of functional peptides with nuclear-targeting activity,can penetrate through biological membranes and target the nucleus and is considered to be a universal tool for constructing nano-drug carrier systems.The use of NLS peptides to construct a functionalized nano-drug carrier system with nuclear targeting ability has important application values in the field of anti-tumor therapy.Although the synthesis process of nuclear-targeted functionalized nano-drug carrier system has been developed,due to the high preparation cost and complex synthesis process,there is still a long research process in the successful translation of nuclear-targeted nanocarriers from the experimental stage to the clinical stage.This review mainly focuses on the composition and construction of the nuclear-targeted functionalized nano-drug carrier system,analyzes its nuclear entry methods and conditions,and prospects the development of the anti-tumor nano-drug carrier system in the future based on the current challenges.

关 键 词：核定位信号 肿瘤 纳米载药体系 

分 类 号：Q5[生物学—生物化学] R943[医药卫生—药剂学]