Research Group of Professor Liu Yu of Nankai University:-Efficient Dynamic Sensing of Biological Mercaptans in Cancer Cells by Cyclodextrin Supramolecular Assemblies

Source: CBG Information

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Introduction

Dynamic monitoring of biological mercaptans in living cells is helpful to deeply understand the pathological or physiological processes related to biological mercaptans. In recent years, fluorescent probes based on Michael addition-elimination mechanism have attracted much attention from researchers. How to realize the targeting of fluorescent probe to cancer cells and improve the sensitivity of dynamic detection is a challenging topic. Recently, Professor Liu Yu's Research Group of Nankai University The use of cyclodextrins has led to new developments in this field ( Chem. Sci. , 2020 11, 4791-4800).

Brief Introduction of Professor Liu Yu

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Liu Yu, Ph.D., Professor of Nankai University, is mainly engaged in the research of organic supramolecular chemistry. In 1994, he was a trans-century talent from the Ministry of Education. In 1996, he was supported by the National Science Fund for Distinguished Young Scholars. In 1997, he was awarded the title of Tianjin Expert and was selected into the Ministry of Personnel in 2000. "One Million Talents Project" , 2010 China Overseas Chinese Contribution Award, 2012 National Outstanding Scientific and Technological Worker, 2006 and 2011 respectively served as the chief scientist of the National 973 Major Research Program. His research results have been published in core journals at home and abroad 5 More than 00 articles, of which the impact factor is greater than 47% of 10.0 Paper SCI Other Cites 1 More than 3000, h-index 62 . He edited 3 monographs and participated in 8 monographs. He won 1 second prize of the National Natural Science Award, 3 first prize of provincial and ministerial natural science, 3 second prize, 1 special prize of Baosteel Excellent Teacher and the National Outstanding Contribution Award for the Implementation of the 11th Five-Year Plan for Science and Technology. He is currently the deputy editor-in-chief of China Chemical Express, Asian J. Org. Chem. The editorial board of 7 magazines, etc.

Frontier scientific research achievements

Efficient Dynamic Sensing of Bio-mercaptans in Cancer Cells by Cyclodextrin Supramolecular Assemblies

Professor Liu Yu's research group of Nankai University has done a lot of work on intelligent assemblies constructed of cyclodextrins. Recently published papers ( Science Advances, 2018 , 4 , Eaat 279; Angew. Chem. Int. Ed. , 2018 , 57 , 8649; Angew. Chem. Int. Ed.   2020 , 59 , 7655; Advanced Science , 2020 ,   10.1002/advs.202000803; Adv. Therap.   2018 , 180013; Chem. Sci. , 2019 , 10 , 3346; Adv. Optical Mater. , 2019 , 1900589; Adv. Mater., 2019 , 1806158;   Chem , 2019 , 5 , 553; Adv. Opt. Mater. , 2017 , 5 , 1700770). On the basis of previous work, the author will Coumarin derivative Modified by a covalent bond to Cyclodextrin On the other hand, by using the hydrogen bond between the hydroxyl group at the small mouth end of cyclodextrin and the biological mercaptan, not only the biological mercaptan is immobilized around cyclodextrin, but also the nucleophilicity of mercapto group is improved, thus realizing the Highly Sensitive Detection of Biological Mercaptan . At the same time, the adamantane modified c-RGD is encapsulated by the host-guest interaction, and the fluorescent probe is endowed with the c-RGD Targeting The ability of cancer cells (Figure 1).

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Fig. 1.-Schematic diagram of reversible detection of bio-mercaptan by cyclodextrin supramolecular assembly

(Source: Chem. Sci. )

RCP-CD has good ratio detection ability for cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) (FIG. 2), giving a lower ratio detection ability for cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) K D Value ( K D [Cys] = 0.172 mM, K D [Hcy] = 0.027 mM, K D [GSH] = 0.059 mM). Compared with coumarin derivatives of unmodified cyclodextrins, K D The value has increased by at least 30 times.  

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Figure 2. Detection Performance of rCP-CD for Biological Mercaptans

(Source: Chem. Sci. )

By comparing the derivatives of different cyclodextrins RCP-CD , RCP-CD (OMe) And RCP-CD @ ADA Yes Detection Performance of Biological Mercaptan , it can be concluded that after the hydroxyl group is methylated, K D Significant increase in value; However, the occupation of cyclodextrin cavities affects the detection performance, indicating that hydroxyl groups around cyclodextrin are the key factors affecting the reaction efficiency. In addition, DFT calculation confirmed that bio-mercaptan can be combined with cyclodextrin through hydrogen bond.

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Figure 3. RCP-CD Detection Performance of Derivatives for Biological Mercaptans

(Source: Chem. Sci. )

RCP-CD @ cRGD-ADA Supramolecular Assemblies and RCP-CD It has the same excellent ratio detection ability for biological mercaptans and gives a lower ratio detection ability for biological mercaptans. K D Value (K D [Cys] = 0.252 mM, K D [Hcy] = 0.027 mM, K D [GSH] = 0.122 mM).

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Figure 4. RCP-CD @ cRGD-ADA Detection Performance of Supramolecular Assemblies for Biological Mercaptans

(Source: Chem. Sci. )

In the process of living cell imaging, relative to RCP-CD , RCP-CD @ cRGD-ADA The supramolecular assembly has Excellent cancer cell targeting . When cancer cells receive external stimuli, they use RCP-CD @ cRGD-ADA The biological mercaptan in living cells can be dynamically monitored in real time.

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Figure 5. RCP-CD @ cRGD-ADA And RCP-CD   Living cell imaging

(Source: Chem. Sci. )

Summary: The author constructed a cyclodextrin supramolecular fluorescent assembly for dynamic monitoring of biological mercaptans in living cells. Structurally, due to the existence of-cyclodextrin, not only the hydroxyl group at the small mouth end is used to form hydrogen bonds with biological mercaptans, but also the sensitivity of fluorescent probe for detection of biological mercaptans is significantly improved; But also greatly improves the solubility and biocompatibility of the fluorescent probe. In addition, it is wrapped by the action of subject and object. CRGD-ADA, Endow RCP-CD @ cRGD-ADA Supramolecular assemblies have excellent cancer cell targeting and realize efficient dynamic monitoring of biological mercaptans in cancer cells. The work was published under the title "High-efficiency dynamic sensing of biothiols in cancer cells with a fluorescent-cyclodextrin supramolecular assembly" in Chem. Sci. ( Chem. Sci. , 2020, 11, 4791-4800).