Citation: Zhao Li-Dong, Zuo Peng, Yin Bin-Cheng, Hong Chenglin, Ye Bang-Ce. A Cell Membrane-Anchored DNA Tetrahedral Sensor for Real-time Monitoring of Exosome Secretion[J]. Acta Chimica Sinica, ;2020, 78(10): 1076-1081. doi: 10.6023/A20060235 shu

A Cell Membrane-Anchored DNA Tetrahedral Sensor for Real-time Monitoring of Exosome Secretion

Zhao Li-Dong ^a ,
Zuo Peng ^a ,
Yin Bin-Cheng ^a,b,, ,
Hong Chenglin ^b,, ,
Ye Bang-Ce ^a,c,,

a.
Lab of Biosystem and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
b.
Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical Engineering, Shihezi University, Shihezi, 832000, China
c.
Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China

Corresponding author: Yin Bin-Cheng, binchengyin@ecust.edu.cn Hong Chenglin, hcl_tea@shzu.edu.cn Ye Bang-Ce, bcye@ecust.edu.cn
Received Date: 14 June 2020
Available Online: 25 July 2020
Fund Project: the National Natural Science Foundation of China 21822402Project supported by the National Natural Science Foundation of China (Nos. 21822402, 21675052, 31730004)the National Natural Science Foundation of China 21675052the National Natural Science Foundation of China 31730004

Figures(11)

Exosomes are nanoscale bilayer membrane vesicles actively secreted by cells, which carry abundant cell-specific substances. They can directly reflect the physiological and functional status of the secreting cells and play important roles in intercellular communication, physiological and pathological processes. In this work, we combined membrane modification technique with fluorescence imaging technique and blended CD63 aptamers into a highly stable and universal DNA tetrahedral structure to construct a cell membrane-anchored DNA sensor for real-time monitoring the secretion of exosomes. We designed four functional toes on each vertex of the tetrahedral sensor, respectively. A signal report toe on the top vertex consisted of fluorophore-modified CD63 aptamer, quencher-modified quencher probe(QP) binding part of the CD63 aptamer, and block probe (BP) binding the rest of the CD63 aptamer. The other three extended toes on the vertices were immobilized to the cell membrane by hybridizing with cholesterol-modified anchor probes(AP), which spontaneously incorporated to a lipid bilayer via hydrophobic interaction between the cholesterol moieties and the cellular membrane. In the initial state, the proposed DNA tetrahedral sensor was tethered to membrane with fluorophores quenched by QP and CD63 aptamer blocked by QP and BP. Trigger probes (TP) were add to bind to BP, resulting in the activation of the sensor. Subsequently, CD63 aptamers were specifically bound to the secreted exosomes, leading to the release of QP and concurrent fluorescence restoration of fluorophore. The intensity of the fluorescent signal in cell membrane was proportional to the amount of exosomes captured, thus realizing the real-time monitoring of the exosomes by analysis the changes of the fluorescence intensity. The experimental results showed that the sensor exhibited a good stability and a high capture efficiency for secreted exosomes. This strategy would provide a potentially useful tool for a variety of applications in biomedical research, drug discovery and tissue engineering.
- cell membrane-anchored sensor,
- DNA tetrahedron,
- exosome,
- secretion,
- real-time monitoring,
- aptamer
1. [1]
  Kowal, J.; Tkach, M.; Théry, C. Curr. Opin. Cell Biol. 2014, 29, 116. doi: 10.1016/j.ceb.2014.05.004
2. [2]
  Shao, H.; Im, H.; Castro, C. M.; Breakefield, X.; Weissleder, R.; Lee, H. Chem. Rev. 2018, 118, 1917. doi: 10.1021/acs.chemrev.7b00534
3. [3]
  Record, M.; Subra, C.; Silventepoirot, S.; Poirot, M. Biochem. Pharmacol. 2011, 81, 1171. doi: 10.1016/j.bcp.2011.02.011
4. [4]
  Johnstone, R. M.; Adam, M.; Hammond, J. R.; Orr, L.; Turbide, C. J. Biol. Chem. 1987, 262, 9412.
5. [5]
  Imjeti, N. S.; Menck, K.; Egea-Jimenez, A. L.; Lecointre, C.; Lembo, F.; Bouguenina, H.; Badache, A.; Ghossoub, R.; David, G.; Roche, S.; Zimmermann, P. Proc. Natl. Acad. Sci. U.S.A. 2017, 114, 12495. doi: 10.1073/pnas.1713433114
6. [6]
  Gallego-Urrea, J. A.; Tuoriniemi, J.; Hassell v, M. TrAC, Trends Anal. Chem. 2011, 30, 473. doi: 10.1016/j.trac.2011.01.005
7. [7]
  Wang, S.; Zhang, L.; Wan, S.; Cansiz, S.; Cui, C.; Liu, Y.; Cai, R.; Hong, C.; Teng, I. T.; Shi, M.; Wu, Y.; Dong, Y.; Tan, W. ACS Nano. 2017, 11, 3943. doi: 10.1021/acsnano.7b00373
8. [8]
  Rupert, D. L.; L sser, C.; Eldh, M.; Block, S.; Zhdanov, V. P.; Lotvall, J. O.; Bally, M.; H k, F. Anal. Chem. 2014, 86, 5929. doi: 10.1021/ac500931f
9. [9]
  Xu, H.; Liao, C.; Zuo, P.; Liu, Z.; Ye, B. C. Anal. Chem. 2018, 90, 13451. doi: 10.1021/acs.analchem.8b03272
10. [10]
  Germain, M.; Balaguer, P.; Nicolas, J. C.; Lopez, F.; Esteve, J. P.; Sukhorukov, G. B.; Winterhalter, M.; Richard-Foy, H.; Fournier, D. Biosens. Bioelectron. 2006, 21, 1566. doi: 10.1016/j.bios.2005.07.011
11. [11]
  Teramura, Y.; Kaneda, Y.; Totani, T.; Iwata, H. Biomaterials. 2008, 29, 1345. doi: 10.1016/j.biomaterials.2007.11.048
12. [12]
  Kim, H.; Shin, K.; Park, O. K.; Choi, D.; Kim, H. D.; Baik, S.; Lee, S. H.; Kwon, S. H.; Yarema, K. J.; Hong, J.; Hyeon, T.; Hwang, N. S. J. Am. Chem. Soc. 2018, 140, 1199. doi: 10.1021/jacs.7b08440
13. [13]
  Chanana, M.; Gliozzi, A.; Diaspro, A.; Chodnevskaja, I.; Huewel, S.; Moskalenko, V.; Ulrichs, K.; Galla, H. J.; Krol, S. Nano Letters. 2005, 5, 2605. doi: 10.1021/nl0521219
14. [14]
  Zhou, W. -Y.; Yang, P. -T.; Yang, R. -H.; Zheng, J. J. Instrum. Anal. 2019, 038, 154 (in Chinese).
15. [15]
  Chen, X.; Zhang, X.; Wang, H. Y.; Chen, Z.; Wu, F. G. Langmuir. 2016, 32, 10126. doi: 10.1021/acs.langmuir.6b02288
16. [16]
  Matsuda, M.; Hatanaka, W.; Takeo, M.; Kim, C. W.; Niidome, T.; Yamamoto, T.; Kishimura, A.; Mori, T.; Katayama, Y. Bioconjug. Chem. 2014, 25, 2134. doi: 10.1021/bc500465j
17. [17]
  Altman, M. O.; Chang, Y. M.; Xiong, X.; Tan, W. Sci. Rep. 2013, 3, 3343. doi: 10.1038/srep03343
18. [18]
  Qiu, L.; Wimmers, F.; Weiden, J.; Heus, H. A.; Tel, J.; Figdor, C. G. Chem. Commun. 2017, 53, 8066. doi: 10.1039/C7CC03576D
19. [19]
  Li, J.; Xun, K.; Pei, K.; Liu, X.; Peng, X.; Du, Y.; Qiu, L.; Tan, W. J. Am. Chem. Soc. 2019, 141, 18013. doi: 10.1021/jacs.9b04725
20. [20]
  Świtalska, A.; Anna, D.; Agnieszka, F. W.; Juskowiak, B. Sensors 2018, 18, 2201. doi: 10.3390/s18072201
21. [21]
  Zeng, S.; Liu, D.; Li, C.; Yu, F.; Fan, L.; Lei, C.; Huang, Y.; Nie, Z.; Yao, S. Anal. Chem. 2018, 90, 13459. doi: 10.1021/acs.analchem.8b03299
22. [22]
  Qiu, L.; Wimmers, F.; Weiden, J.; Heus, H. A.; Tel, J.; Figdor, C. G. Chem. Commun. 2017, 53, 8066. doi: 10.1039/C7CC03576D
23. [23]
  Yuan, J.; Deng, Z.; Liu, H.; Li, X.; Li, J.; He, Y.; Qing, Z.; Yang, Y.; Zhong, S. ACS Sens. 2019, 4, 1648. doi: 10.1021/acssensors.9b00482
24. [24]
  Goodman, R. P.; Berry, R. M.; Turberfield, A. J. Chem. Commun. 2004, 12, 1372.
25. [25]
  Schlapak, R.; Danzberger, J.; Armitage, D.; Morgan, D.; Ebner, A.; Hinterdorfer, P.; Pollheimer, P.; Gruber, H. J.; Sch ffler, F.; Howorka, S. Small 2012, 8, 89. doi: 10.1002/smll.201101576
26. [26]
  Ye, D.-K.; Zuo, X.-L.; Fan, C.-H. Prog. Chem. 2017, 01, 36 (in Chinese).
27. [27]
  Chen, X.; Zhou, G.; Song, Ping.; Wang, J.; Gao, J.; Lu, J.; Fan, C.; Zuo, X. Anal. Chem. 2014, 86, 7337. doi: 10.1021/ac500054x
28. [28]
  Zhu, F.-L.; Bian, X.-J.; Tian, R.; Li, L.; Yan, J.; Liu, G. Chin. J. Anal. Chem. 2020, 4, 473 (in Chinese).
29. [29]
  He, L.; Lu, D.; Liang, H.; Xie, S.; Zhang, X.; Liu, Q.; Yuan, Q.; Tan, W. J. Am. Chem. Soc. 2018, 140, 258. doi: 10.1021/jacs.7b09789
30. [30]
  Conway, J. W.; Madwar, C.; Edwardson, T. G.; McLaughlin, C. K.; Fahkoury, J.; Lennox, R. B.; Sleiman, H. F. J. Am. Chem. Soc. 2014, 136, 12987. doi: 10.1021/ja506095n
31. [31]
  Lin, M.; Wang, J.; Zhou, G.; Wang, J.; Wu, N.; Lu, J.; Gao, J.; Chen, X.; Shi, J.; Zuo, X.; Fan, C. Angew. Chem. Int. Ed. 2015, 54, 2151. doi: 10.1002/anie.201410720
1. [1]
  Qilong Fang , Yiqi Li , Jiangyihui Sheng , Quan Yuan , Jie Tan . Magical Pesticide Residue Detection Test Strips: Aptamer-based Lateral Flow Test Strips for Organophosphorus Pesticide Detection. University Chemistry, 2024, 39(5): 80-89. doi: 10.3866/PKU.DXHX202310004
2. [2]
  Gonglan Ye , Xia Yin , Feng Xu , Peng Yang , Yingpeng Wu , Huilong Fei . Innovations in “Four-in-One” Inorganic Chemistry Education. University Chemistry, 2024, 39(8): 136-141. doi: 10.3866/PKU.DXHX202401071
3. [3]
  Jiahong ZHENG , Jingyun YANG . Preparation and electrochemical properties of hollow dodecahedral CoNi₂S₄ supported by MnO₂ nanowires. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1881-1891. doi: 10.11862/CJIC.20240170
4. [4]
  Qiaoqiao BAI , Anqi ZHOU , Xiaowei LI , Tang LIU , Song LIU . Construction of pressure-temperature dual-functional flexible sensors and applications in biomedicine. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2259-2274. doi: 10.11862/CJIC.20240128
5. [5]
  Xingchao Zhao , Xiaoming Li , Ming Liu , Zijin Zhao , Kaixuan Yang , Pengtian Liu , Haolan Zhang , Jintai Li , Xiaoling Ma , Qi Yao , Yanming Sun , Fujun Zhang . 倍增型全聚合物光电探测器及其在光电容积描记传感器上的应用. Acta Physico-Chimica Sinica, 2025, 41(1): 2311021-. doi: 10.3866/PKU.WHXB202311021
6. [6]
  Jiarong Feng , Yejie Duan , Chu Chu , Dezhen Xie , Qiu'e Cao , Peng Liu . Preparation and Application of a Streptomycin Molecularly Imprinted Electrochemical Sensor: A Suggested Comprehensive Analytical Chemical Experiment. University Chemistry, 2024, 39(8): 295-305. doi: 10.3866/PKU.DXHX202401016
7. [7]
  Meiqing Yang , Lu Wang , Haozi Lu , Yaocheng Yang , Song Liu . Recent Advances of Functional Nanomaterials for Screen-Printed Photoelectrochemical Biosensors. Acta Physico-Chimica Sinica, 2025, 41(2): 100018-. doi: 10.3866/PKU.WHXB202310046
8. [8]
  Min LIU , Huapeng RUAN , Zhongtao FENG , Xue DONG , Haiyan CUI , Xinping WANG . Neutral boron-containing radical dimers. Chinese Journal of Inorganic Chemistry, 2025, 41(1): 123-130. doi: 10.11862/CJIC.20240362
9. [9]
  Zhongxin YU , Wei SONG , Yang LIU , Yuxue DING , Fanhao MENG , Shuju WANG , Lixin YOU . Fluorescence sensing on chlortetracycline of a Zn-coordination polymer based on mixed ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2415-2421. doi: 10.11862/CJIC.20240304
10. [10]
  Linjie ZHU , Xufeng LIU . Electrocatalytic hydrogen evolution performance of tetra-iron complexes with bridging diphosphine ligands. Chinese Journal of Inorganic Chemistry, 2025, 41(2): 321-328. doi: 10.11862/CJIC.20240207
11. [11]
  Xingyuan Lu , Yutao Yao , Junjing Gu , Peifeng Su . Energy Decomposition Analysis and Its Application in the Many-Body Effect of Water Clusters. University Chemistry, 2025, 40(3): 100-107. doi: 10.12461/PKU.DXHX202405074
12. [12]
  Xiao SANG , Qi LIU , Jianping LANG . Synthesis, structure, and fluorescence properties of Zn(Ⅱ) coordination polymers containing tetra-alkenylpyridine ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(11): 2124-2132. doi: 10.11862/CJIC.20240158
13. [13]
  Liang TANG , Jingfei NI , Kang XIAO , Xiangmei LIU . Synthesis and X-ray imaging application of lanthanide-organic complex-based scintillators. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1892-1902. doi: 10.11862/CJIC.20240139
14. [14]
  Chengbin Gong , Guona Zhang , Qian Tang , Hong Lei , Ling Kong , Wenshan Ren . Development of a Practical Teaching System for the Applied Chemistry Major Emphasizing “Industry-Education Integration, University-Enterprise Cooperation, and Multi-Dimensional Combination”. University Chemistry, 2024, 39(6): 220-225. doi: 10.3866/PKU.DXHX202309104
15. [15]
  Jiaxuan Zuo , Kun Zhang , Jing Wang , Xifei Li . 锂离子电池Ni-Co-Mn基正极材料前驱体的形核调控及机制. Acta Physico-Chimica Sinica, 2025, 41(1): 2404042-. doi: 10.3866/PKU.WHXB202404042
16. [16]
  Qiqi Li , Su Zhang , Yuting Jiang , Linna Zhu , Nannan Guo , Jing Zhang , Yutong Li , Tong Wei , Zhuangjun Fan . 前驱体机械压实制备高密度活性炭及其致密电容储能性能. Acta Physico-Chimica Sinica, 2025, 41(3): 2406009-. doi: 10.3866/PKU.WHXB202406009
17. [17]
  Youlin SI , Shuquan SUN , Junsong YANG , Zijun BIE , Yan CHEN , Li LUO . Synthesis and adsorption properties of Zn(Ⅱ) metal-organic framework based on 3, 3', 5, 5'-tetraimidazolyl biphenyl ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1755-1762. doi: 10.11862/CJIC.20240061
18. [18]
  Xiping Luo , Xing Wang , Shengxiang Yang , Jianzhong Guo , Yuxuan Wang , Xuejuan Yang . Innovative “One Body, Dual Wings” Embedded Talent Cultivation Model: Practice in the Construction of Applied Chemistry Major at Zhejiang Agriculture and Forestry University. University Chemistry, 2024, 39(3): 205-209. doi: 10.3866/PKU.DXHX202309058
19. [19]
  Lijun Huo , Mingcun Wang , Tianyi Zhao , Mingjie Liu . Exploration of Undergraduate and Graduate Integrated Teaching in Polymer Chemistry with Aerospace Characteristics. University Chemistry, 2024, 39(6): 103-111. doi: 10.3866/PKU.DXHX202312059
20. [20]
  Li Zhou , Dongyan Tang , Yunchen Du . Focusing on the Cultivation of Outstanding Talents: A “Five in One” Approach to Promoting the Construction of Chemical Experimental and Practical Teaching System. University Chemistry, 2024, 39(7): 121-128. doi: 10.12461/PKU.DXHX202405037

Get Citation

PDF

XML

Metrics

PDF Downloads(20)
Abstract views(1742)
HTML views(455)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142