Citation: Zhenni Lin, Bangping Hu, Qinian Liu, Yujie Huang, Xing-Can Shen, Hua Chen. Electronic tuning of cyanine for highly specific dual ratiometric NIR-Ⅱ fluorescence/photoacoustic imaging of H₂S₂ in vivo[J]. Chinese Chemical Letters, ;2026, 37(12): 112339. doi: 10.1016/j.cclet.2025.112339 shu

Electronic tuning of cyanine for highly specific dual ratiometric NIR-Ⅱ fluorescence/photoacoustic imaging of H₂S₂ in vivo

Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Guangxi Key Laboratory of Chemistry and Molecular Engineering of Medicinal Resources, University Engineering Research Center for Chemistry of Characteristic Medicinal Resources (Guangxi), School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China

xcshen@mailbox.gxnu.edu.cn

chenhuagnu@gxnu.edu.cn

Received Date: 11 November 2025
Revised Date: 24 December 2025
Accepted Date: 28 December 2025
Available Online: 29 December 2025

Figures(7)

Given the critical role of hydrogen persulfide (H₂S₂) in biological systems, its accurate quantification and visualization within deep tissues are essential for understanding associated pathophysiological processes. However, conventional hydrogen polysulfide probes often suffer from inadequate selectivity among reactive sulfur species, limiting their reliability for quantitative imaging applications. Herein, we developed a novel dual ratiometric near-infrared-Ⅱ (NIR-Ⅱ) fluorescence/photoacoustic probe for deep imaging of H₂S₂ with unprecedented specificity through electronic tuning of cyanine. Strong electron-donating moieties were responsible for modulating the specific responsiveness to H₂S₂ over H₂S. Such a designed probe (H₂S₂–4) exhibited robust dual-ratiometric NIR-Ⅱ fluorescence (I₈₉₀/I₁₀₂₀, 42-fold) and photoacoustic (PA₈₄₀/PA₉₆₀, 4.49-fold) responses towards Na₂S₂ species with high specificity and sensitivity. By use of dual ratiometric NIR-Ⅱ fluorescence/photoacoustic imaging, we successfully mapped endogenous H₂S₂ fluctuations in bacterial infection-induced inflammation models in vivo with enhanced accuracy and reliability. Thus, this study not only provides a versatile tool for dissecting H₂S₂-related biological events but also establishes an electronic-tuning strategy to guide the design of advanced H₂S₂-specific probes.
- Electronic tuning strategy,
- Cyanine,
- Dual ratiometric imaging,
- NIR-Ⅱ,
- H₂S₂ probe
1. [1]
  G.K. Kolluru, R.E. Shackelford, X. Shen, et al., Nat. Rev. Cardiol. 20 (2023) 109–125. doi: 10.1038/s41569-022-00741-6
2. [2]
  X. Chen, Y. Zhou, X. Peng, et al., Chem. Soc. Rev. 39 (2010) 2120–2135. doi: 10.1039/b925092a
3. [3]
  D. Fass, C. Thorpe, Chem. Rev. 118 (2018) 1169–1198. doi: 10.1021/acs.chemrev.7b00123
4. [4]
  G. Yang, L. Wu, B. Jiang, et al., Science 322 (2008) 587–590. doi: 10.1126/science.1162667
5. [5]
  M.R. Filipovic, J. Zivanovic, B. Alvarez, et al., Chem. Rev. 118 (2017) 1253–1337.
6. [6]
  A.V. Mishanina, M. Libiad, R. Banerjee, Nat. Chem. Biol. 11 (2015) 457–464. doi: 10.1038/nchembio.1834
7. [7]
  B.C. Yu, Y.Q. Zheng, Z.N. Yuan, et al., J. Am. Chem. Soc. 140 (2018) 30–33. doi: 10.1021/jacs.7b09795
8. [8]
  K.R. Olson, Y. Gao, F. Arif, et al., Redox Biol. 15 (2018) 74–85. doi: 10.1016/j.redox.2017.11.009
9. [9]
  R. Wang, Physiol. Rev. 92 (2012) 791–896. doi: 10.1152/physrev.00017.2011
10. [10]
  T.S. Bailey, M.D. Pluth, J. Am. Chem. Soc. 135 (2013) 16697–16704. doi: 10.1021/ja408909h
11. [11]
  T. Ida, T. Sawa, H. Ihara, et al., Proc. Natl. Acad. Sci. U. S. A. 111 (2014) 7606–7611. doi: 10.1073/pnas.1321232111
12. [12]
  P.K. Yadav, M. Martinov, V. Vitvitsky, et al., J. Am. Chem. Soc. 138 (2016) 289–299. doi: 10.1021/jacs.5b10494
13. [13]
  C.E. Paulsen, K.S. Carroll, Chem. Rev. 113 (2013) 4633–4679. doi: 10.1021/cr300163e
14. [14]
  H. Liu, M.N. Radford, C.T. Yang, et al., Br. J. Pharmacol. 176 (2019) 616–627. doi: 10.1111/bph.14330
15. [15]
  N. Sen, B.D. Paul, M.M. Gadalla, et al., Mol. Cell 45 (2012) 13–24. doi: 10.1016/j.molcel.2011.10.021
16. [16]
  D.H. Zhang, I. Macinkovic, N.O. Devarie-Baez, et al., Angew. Chem. Int. Ed. 53 (2014) 575–581. doi: 10.1002/anie.201305876
17. [17]
  H. Dong, Q. Zhou, L. Zhang, et al., Angew. Chem. Int. Ed. 58 (2019) 13948–13953. doi: 10.1002/anie.201907210
18. [18]
  C. Debiemme-Chouvy, C. Wartelle, F.X. Sauvage, J. Phys. Chem. B 108 (2004) 18291–18296. doi: 10.1021/jp046977y
19. [19]
  J. Gun, A.D. Modestov, A. Kamyshny, et al., Microchim. Acta 146 (2004) 229–237. doi: 10.1007/s00604-004-0179-5
20. [20]
  S. Koike, K. Kawamura, Y. Kimura, et al., Free Radic. Biol. Med. 113 (2017) 355–362. doi: 10.1016/j.freeradbiomed.2017.10.346
21. [21]
  M. Yang, J. Fan, J. Du, et al., Chem. Sci. 11 (2020) 5127–5141. doi: 10.1039/d0sc01482f
22. [22]
  Y. Yao, J. Chen, C. Yan, et al., J. Am. Chem. Soc. 147 (2025) 46953–46965. doi: 10.1021/jacs.5c10749
23. [23]
  C. Yan, C. Liu, B. Liu, et al., Nat. Aging 5 (2025) 2532–2545. doi: 10.1038/s43587-025-01001-1
24. [24]
  Y. Huang, L. Wang, Q. Huang, et al., Chin. J. Chem. 43 (2025) 2603–2612. doi: 10.1002/cjoc.70160
25. [25]
  M. Xian, Y. Wang, C. Du, et al., Acc. Chem. Res. 58 (2025) 2804–2814. doi: 10.1021/acs.accounts.5c00483
26. [26]
  K.G. Fosnacht, M.D. Pluth, Chem. Rev. 124 (2024) 4124–4257. doi: 10.1021/acs.chemrev.3c00683
27. [27]
  X. Zhang, Y. Yang, L. Zhang, et al., Talanta 268 (2024) 125293. doi: 10.1016/j.talanta.2023.125293
28. [28]
  Y. Zhou, Z. Gu, C. Liu, et al., Angew. Chem. Int. Ed. 61 (2022) e202114504. doi: 10.1002/anie.202114504
29. [29]
  X. Zhang, L. Zhang, M. Gao, et al., J. Hazard. Mater. 396 (2020) 122673. doi: 10.1016/j.jhazmat.2020.122673
30. [30]
  X. Luo, C. Zhang, C. Yue, et al., Chem. Sci. 14 (2023) 14290–14301. doi: 10.1039/d3sc04937j
31. [31]
  J. Franz, M. Oelschlegel, J.P. Zobel, et al., J. Am. Chem. Soc. (2024) 11272–11288.
32. [32]
  J. Zhang, M. He, M. Huang, et al., Angew. Chem. Int. Ed. 64 (2025) e202519021. doi: 10.1002/anie.202519021
33. [33]
  X. Tan, J. Zhou, L. Yang, et al., J. Am. Chem. Soc. 146 (2024) 30422–30433. doi: 10.1021/jacs.4c10266
34. [34]
  Z. Zheng, J. Gao, R. Wang, et al., ACS Nano 17 (2023) 22060–22070. doi: 10.1021/acsnano.3c08767
35. [35]
  Z. Lv, J. Wang, J. Xu, et al., Adv. Healthcare Mater. 14 (2025) 2500273. doi: 10.1002/adhm.202500273
36. [36]
  C. Liu, W. Chen, W. Shi, et al., J. Am. Chem. Soc. 136 (2014) 7257–7260. doi: 10.1021/ja502968x
37. [37]
  J. Guo, S. Yang, C. Guo, et al., Anal. Chem. 90 (2017) 881–887.
38. [38]
  W. Chen, E.W. Rosser, T. Matsunaga, et al., Angew. Chem. Int. Ed. 54 (2015) 13961–13965. doi: 10.1002/anie.201506887
39. [39]
  B. Hu, Q. Liu, Y. Jiang, et al., Angew. Chem. Int. Ed. 64 (2025) e202418378. doi: 10.1002/anie.202418378
40. [40]
  L. Sun, Z. Zheng, Z. Zhang, et al., Anal. Chem. 96 (2024) 20049–20056. doi: 10.1021/acs.analchem.4c04848
41. [41]
  C. Zhao, X. Yang, Chin. J. Org. Chem. 45 (2025) 1419–1420. doi: 10.2147/copd.s503625
42. [42]
  R.R. Zhang, X.Y. Ran, K.K. Yu, et al., Adv. Mater. 37 (2025) 2415891. doi: 10.1002/adma.202415891
43. [43]
  W. Pan, M. Rafiq, W. Haider, et al., Coord. Chem. Rev. 514 (2024) 215907. doi: 10.1016/j.ccr.2024.215907
44. [44]
  Y. Xu, C. Li, R. Xu, et al., Chem. Sci. 11 (2020) 8157–8166. doi: 10.1039/d0sc03160g
45. [45]
  J. Huang, K. Pu, Angew. Chem. Int. Ed. 59 (2020) 11717–11731. doi: 10.1002/anie.202001783
46. [46]
  B. Li, H. Liu, M. Zhao, et al., Angew. Chem. Int. Ed. 63 (2024) e202404093. doi: 10.1002/anie.202404093
47. [47]
  Y. Zhang, S. Lei, Y. Pan, et al., Chin. Chem. Lett. 37 (2026) 110977. doi: 10.1016/j.cclet.2025.110977
48. [48]
  H. Liu, Q. Sun, M. Dong, et al., Chin. Chem. Lett. 37 (2026) 111655. doi: 10.1016/j.cclet.2025.111655
49. [49]
  K. Buscher, H. Wang, X. Zhang, et al., Nat. Commun. 7 (2016) 10828. doi: 10.1038/ncomms10828
50. [50]
  Y. He, X. Wang, S. He, et al., ACS Nano 19 (2025) 6977–6992. doi: 10.1021/acsnano.4c14689
51. [51]
  F. Di Lorenzo, K.A. Duda, R. Lanzetta, et al., Chem. Rev. 122 (2022) 15767–15821. doi: 10.1021/acs.chemrev.0c01321
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2. [2]
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通讯作者: 陈斌, bchen63@163.com

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沈阳化工大学材料科学与工程学院沈阳 110142

Electronic tuning of cyanine for highly specific dual ratiometric NIR-Ⅱ fluorescence/photoacoustic imaging of H2S2 in vivo

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通讯作者: 陈斌, bchen63@163.com

Electronic tuning of cyanine for highly specific dual ratiometric NIR-Ⅱ fluorescence/photoacoustic imaging of H₂S₂ in vivo