基于双硫键的荧光传感器在生物检测及靶向治疗药物输送系统中的应用  

The Application of Disulfide-based Fluorescent Sensor in Biological Detection and Targeted Theranostic Drug Delivery

作　　者：张晓琳 丰晓婷 詹世平[1,2] 卢春兰 李鸣明[1,2] 侯维敏 ZHANG Xiaolin;FENG Xiaoting;ZHAN Shiping;LU Chunlan;LI Mingming;HOU Weimin(College of Environmental and Chemical Engineering,Dalian University,Dalian 116622,China;Chemical and Environmental Protection Engineering Research Technology Center,Dalian 116622,China)

机构地区：[1]大连大学环境与化学工程学院,大连116622 [2]辽宁省化工环保工程技术研究中心,大连116622

出　　处：《材料导报》2020年第5期142-147,共6页Materials Reports

基　　金：辽宁省自然科学基金指导计划项目(201602036);国家自然科学基金(21102014)~~

摘　　要：谷胱甘肽几乎存在于身体的每一个细胞,是细胞内重要的调节代谢物质,对维持人体内正常的免疫系统及生化防御体系不可或缺,实时快速地实现谷胱甘肽的检测对疾病的监控以及早期诊断治疗具有重要意义。基于双硫键的荧光传感器可对细胞内谷胱甘肽实现荧光检测,响应迅速,灵敏度高,得到了研究人员的普遍关注。基于双硫键的荧光传感器不仅可通过荧光强度实现对谷胱甘肽的荧光检测,近年来还实现了对谷胱甘肽的比率荧光检测,避免了生物体内背景荧光的干扰。但是大多数荧光传感器在生物体内检测没有靶向性并且只能单纯地实现硫醇含量的荧光检测,而在硫醇含量远超过正常细胞的肿瘤细胞内,更迫切需要实现的是在诊断后实现肿瘤治疗。近年来,研究者们在这方面做了大量的工作,并取得了丰硕的成果,经过巧妙设计将基于双硫键的荧光传感器与抗肿瘤药物、肿瘤细胞靶向单元有机结合,实现了集诊断与治疗为一体的、基于双硫键的荧光传感器。该类荧光传感器若要同时实现荧光信号诊断与靶向肿瘤释放药物,四个重要的元素不可或缺:(1)荧光信号;(2)可切断的连接;(3)靶向配体;(4)抗肿瘤药物。这类荧光传感器设计关键就是可切断的连接,而双硫键在肿瘤细胞内高浓度的谷胱甘肽环境中能够实现双硫键的断裂,成为设计的核心环节。当双硫键断裂后可实现抗肿瘤药物(如喜树碱、阿霉素、胞苷和顺铂等)的释放。通过引入性能优异的荧光发色团可实现双硫键断裂前后荧光信号的变化,为降低对生物体的损伤,近红外荧光团如氟硼吡咯和菁类等荧光团受到了更多的关注。靶向配体则选择了叶酸、半乳糖、维生素等局部定位基团靶向肿瘤细胞,靶向性的提高极大降低了药物的副作用。近年来该领域发展迅速,不仅能实现靶向肿瘤释放药物的个性化治�Glutathione,which exists in almost every cell of the body,is an important regulatory metabolite in the cell and indispensable for maintaining the normal immune system and biochemical defense system in the human body.Detection of glutathione in real time and quickly is of great significance for disease monitoring and early diagnosis and treatment.Fluorescence sensor based on disulfide bond has received considerable attention due to its rapid response to intracellular glutathione with high sensitivity.Fluorescence sensor based on disulfide bond can not only detect glutathione by fluorescence intensity,but also detect glutathione by ratio fluorescence to avoid interference of background fluorescence in vivo.However,most fluorescence sensors can only achieve the fluorescence detection of thiol content and cannot obtain targeted therapy.At present,in tumor cells with far higher thiol content than normal cells,it is more urgent to realize tumor treatment after diagnosis.In recent years,researchers have done a lot of work in this field and achieved fruitful results.Through ingenious design,fluorescence sensors based on bisulfide bond were designed to combine with anti-tumor drugs within one molecular system to achieve disease diagnosis and treatment.The fluorescent sensor that allows targeted therapeutic release and imaging simultaneously,contains the following elements:ⅰ.fluorescent reporters,ⅱ.cleavable linkers,ⅲ.cancer targeting ligands,ⅳ.masked chemotherapeutic agents.The cleavable disulfide bonds,as the key of designing such fluorescent sensors,can be efficiently cleaved in the high concentration of glutathione in tumor cells to release antitumor drugs(such as camptothecin,adriamycin,cytidine and cisplatin).Excellent fluorophores that have proved attractive for constructing disulfide-based sensors include naphthalimide,coumarin,BODIPY,near-infrared CY7 and so on.The tumor targeting capability may be enhanced by attaching to specific site-localizing entities,such as folate,galactose,vitamin and other local l

关 键 词：双硫键 靶向药物 荧光传感器 谷胱甘肽 生物检测 

分 类 号：O69[理学—化学]