The Application of Disulfide-based Fluorescent Sensor in Biological Detection and Targeted Theranostic Drug Delivery
ZHANG Xiaolin1,2, FENG Xiaoting1,2, ZHAN Shiping1,2, LU Chunlan1,2, LI Mingming1,2, HOU Weimin1,2
1 College of Environmental and Chemical Engineering, Dalian University, Dalian 116622, China; 2 Chemical and Environmental Protection Engineering Research Technology Center, Dalian 116622, China
Abstract: 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 localization groups, which display intrinsic selectivity for can-cer cells over normal cells due to their genetic signatures or because of an overexpression of specific receptors on certain tumor cells. With the rapid development in this field, disulfide-based fluorescent sensors can not only achieve personalized treatment of targeted tumor release drugs, but also monitor the drug release process by fluorescence signal. This review gives a retrospection of the research efforts with respect to the fluorescence sensors based on disulfide bond and targeting drug delivery system, and expounds simply its application in biological imaging and drug delivery, to further deepen the understanding of cell uptake and drug release mechanism. The aim is to promote the further development of molecular design of intracellular fluorescence detection sensors and drug delivery systems.
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2020, Vol. 34 
