journal article·2024-12-18

Fluorogenic Labeling Probe for the Imaging of Endogenous β-Galactosidase Activity in Cancer and Senescent Cells

Jing-Bo Wang, Xue-Ru Zhao, Xi-Le Hu, Yi Zang, Jia Li, Xiao-Peng He

ACS Applied Materials & Interfaces· Volume 16· Issue 50
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Abstract

The sensitive detection of glycosidases in live cells is crucial to understanding their functional roles in disease progression. Here, we develop a fluorogenic labeling probe for β-galactosidase (β-Gal) based on a bright green-emitting fluorescent dye, fluorescein. Galactose was introduced to a fluoromethyl-substituted fluorescein derivative through a benzyl spacer, resulting in a quenched fluorescence due to spirocyclization of the dye. After removal of the galactosyl residue by β-Gal, an ∼210-fold enhanced green fluorescence (emission maximum at 524 nm) was detected, and the presence of other glycosidases and hydrolases did not produce false-positive signals. The probe was successfully used for imaging of the endogenous β-Gal activity in cancer and senescent cells, and the imaging results agree with the β-Gal expression level of the cells, as determined by Western blotting and polymerase chain reaction. Importantly, we demonstrated that upon hydrolysis of galactose, the fluoromethyl-substituted fluorescein derivative is covalently attached to adjacent proteins, both in solution and in live cells. This study offers a small-molecule probe for the sensitive monitoring of endogenous glycosidase activity.
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Research context

OpenAlex topics: Photoreceptor and optogenetics research · Nanoplatforms for cancer theranostics · Advanced biosensing and bioanalysis techniques

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 130 Meilong Rd., Shanghai 200237, China

State Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

Lingang Laboratory, Shanghai 201203, China

National Center for Liver Cancer, the International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China

Funding

Project 211 · State Key Laboratory of Drug Research, Chinese Academy of Sciences · State Key Laboratory of Chemo/Biosensing and Chemometrics · State Key Laboratory of Bioreactor Engineering · Fundamental Research Funds for the Central Universities · National Natural Science Foundation of China · International Cooperation Program of Shanghai Science and Technology · Ministry of Education Key Laboratory on signaling Regulation and Targeting Therapy of Liver Cancer

References (63)

Show source-provided references
1. 10.1038/s41571-021-00514-z10.1038/s41571-021-00514-z ↗
2. 10.1038/s41568-024-00708-410.1038/s41568-024-00708-4 ↗
3. 10.1038/nrc164910.1038/nrc1649 ↗
4. 10.1038/nrc398210.1038/nrc3982 ↗
5. 10.1007/BF0004773810.1007/BF00047738 ↗
6. 10.1002/smll.20110193810.1002/smll.201101938 ↗
7. 10.1186/1471-2288-3-2510.1186/1471-2288-3-25 ↗
8. 10.1021/bc700216d10.1021/bc700216d ↗
9. 10.1016/j.ab.2003.11.01210.1016/j.ab.2003.11.012 ↗
10. 10.1016/j.exger.2005.07.01110.1016/j.exger.2005.07.011 ↗
11. 10.1039/C7CS00240H10.1039/C7CS00240H ↗
12. 10.1021/acs.chemrev.6b0000110.1021/acs.chemrev.6b00001 ↗
13. 10.1002/anie.20200979610.1002/anie.202009796 ↗
14. 10.1039/D3CS00032J10.1039/D3CS00032J ↗
15. 10.1039/C7CS00862G10.1039/C7CS00862G ↗
16. 10.1021/acs.chemrev.3c0061210.1021/acs.chemrev.3c00612 ↗
17. 10.1021/acs.analchem.2c0470510.1021/acs.analchem.2c04705 ↗
18. 10.1002/anie.20210127810.1002/anie.202101278 ↗
19. 10.1021/jacs.6b0170510.1021/jacs.6b01705 ↗
20. 10.1016/j.cclet.2023.10832110.1016/j.cclet.2023.108321 ↗
21. 10.1039/C6CC04373A10.1039/C6CC04373A ↗
22. 10.1002/anie.20231313710.1002/anie.202313137 ↗
23. 10.1021/acssensors.1c0163010.1021/acssensors.1c01630 ↗
24. 10.1002/agt2.28610.1002/agt2.286 ↗
25. 10.1039/C6QM00112B10.1039/C6QM00112B ↗
26. 10.1021/acs.analchem.1c0563510.1021/acs.analchem.1c05635 ↗
27. 10.1021/acs.analchem.7b0481310.1021/acs.analchem.7b04813 ↗
28. 10.1021/acs.analchem.3c0007510.1021/acs.analchem.3c00075 ↗
29. 10.3389/fchem.2022.91962410.3389/fchem.2022.919624 ↗
30. 10.1021/acsmaterialslett.2c0111210.1021/acsmaterialslett.2c01112 ↗
31. 10.1039/C8CC10311A10.1039/C8CC10311A ↗
32. 10.1021/ja043919h10.1021/ja043919h ↗
33. 10.1021/ja067710a10.1021/ja067710a ↗
34. 10.1039/D1SC02259H10.1039/D1SC02259H ↗
35. 10.1039/D1SC05057E10.1039/D1SC05057E ↗
36. 10.1021/acs.analchem.9b0383210.1021/acs.analchem.9b03832 ↗
37. 10.1016/j.snb.2023.13454110.1016/j.snb.2023.134541 ↗
38. 10.1039/D3QO00605K10.1039/D3QO00605K ↗
39. 10.1021/jacs.0c0537910.1021/jacs.0c05379 ↗
40. 10.1038/s41589-021-00960-x10.1038/s41589-021-00960-x ↗
41. 10.1073/pnas.220055311910.1073/pnas.2200553119 ↗
42. 10.1021/jacs.7b0194810.1021/jacs.7b01948 ↗
43. 10.1002/anie.20230930610.1002/anie.202309306 ↗
44. 10.1021/ja510673810.1021/ja5106738 ↗
45. 10.1039/D1CS00543J10.1039/D1CS00543J ↗
46. 10.1002/anie.20100570510.1002/anie.201005705 ↗
47. 10.1021/ja062948k10.1021/ja062948k ↗
48. 10.1038/nchembio70710.1038/nchembio707 ↗
49. 10.1038/nchembio72810.1038/nchembio728 ↗
50. 10.1002/anie.20100015010.1002/anie.201000150 ↗
51. 10.1002/anie.20160332810.1002/anie.201603328 ↗
52. 10.3390/molecules2524596410.3390/molecules25245964 ↗
53. 10.1016/j.bmcl.2019.12686010.1016/j.bmcl.2019.126860 ↗
54. 10.1039/C9CC07903C10.1039/C9CC07903C ↗
55. 10.1073/pnas.201851311810.1073/pnas.2018513118 ↗
56. 10.1038/s43587-023-00360-x10.1038/s43587-023-00360-x ↗
57. 10.1186/s12931-024-02777-310.1186/s12931-024-02777-3 ↗
58. 10.1038/nprot.2009.19110.1038/nprot.2009.191 ↗
59. 10.4161/cc.2494410.4161/cc.24944 ↗
60. 10.1038/s41580-024-00738-810.1038/s41580-024-00738-8 ↗
61. 10.1007/978-1-62703-788-4_910.1007/978-1-62703-788-4_9 ↗
62. 10.1016/j.cell.2017.07.04910.1016/j.cell.2017.07.049 ↗
63. 10.1073/pnas.201851311810.1073/pnas.2018513118 ↗