Skip to main content
SpringerLink
Log in

Raman imaging analysis of intracellular biothiols independent of the aggregation of sensing substrates

  • Articles
  • Published:
Science China Chemistry Aims and scope Submit manuscript

Abstract

The content of biothiols in cells is highly associated with the occurrence and development of several diseases. However, due to their active chemical properties, thiol-contained molecules are normally volatile during the detection process, rendering precise analysis of intracellular biothiols challenging. In this study, 5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB) is covalently modified on the surface of gold nanorods (AuNRs), constructing sensing substrates for in situ Raman imaging analysis of biothiols in cells. AuNRs are able to serve as ideal surface-enhanced Raman scattering substrates, and thus Raman signals of DTNB are greatly amplified by AuNRs. Meanwhile, the disulfide bond of DTNB can be broken by thiols, thereby releasing part of DTNB from the surface of AuNRs. As a result, three kinds of main biothiols are sensitively quantified with DTNB-modified AuNRs according to the variation of Raman signals, and DTNB-modified AuNRs exhibit far better analytical performance than a commercial probe. In addition, the sensing substrates can be readily delivered to cytoplasm with the transmembrane of AuNRs, and are capable of responding to biothiols in cells. Notably, the Raman approach is established by the breaking of chemical bonds rather than the aggregation of substrates, which is more inclined to analyze intracellular biothiols with a desirable spatial resolution. Therefore, fluctuation of biothiols in glioma cells is evidently observed via Raman imaging. Overall, this work provides an alternative strategy for designing Raman sensors to visualize active molecules in cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Caneque T, Müller S, Rodriguez R. Nat Rev Chem, 2018, 2: 202–215

    Article  Google Scholar 

  2. Walsh CT, Tu BP, Tang Y. Chem Rev, 2018, 118: 1460–1494

    Article  CAS  PubMed  Google Scholar 

  3. Malla JA, Umesh RM, Yousf S, Mane S, Sharma S, Lahiri M, Talukdar P. Angew Chem Int Ed, 2020, 59: 7944–7952

    Article  CAS  Google Scholar 

  4. Wiley CD, Campisi J. NatMetab, 2021, 3: 1290–1301

    CAS  Google Scholar 

  5. Fang H, Chen Y, Wang Y, Geng S, Yao S, Song D, He W, Guo Z. Sci China Chem, 2020, 63: 699–706

    Article  CAS  Google Scholar 

  6. Wu L, Liu J, Li P, Tang B, James TD. Chem Soc Rev, 2021, 50: 702–734

    Article  CAS  PubMed  Google Scholar 

  7. Guo T, Chen X, Qu W, Yang B, Tian R, Geng Z, Wang Z. Anal Chem, 2022, 94: 5006–5013

    Article  CAS  PubMed  Google Scholar 

  8. Guan X, Hoffman B, Dwivedi C, Matthees DP. J Pharm BiomedAnal, 2003, 31: 251–261

    Article  CAS  Google Scholar 

  9. Gong Z, Liu Z, Zhang Z, Mei Y, Tian Y. CCS Chem, 2022, 4: 2020–2030

    Article  CAS  Google Scholar 

  10. Zhu R, Feng H, Li Q, Su L, Fu Q, Li J, Song J, Yang H. Angew Chem IntEd, 2021, 60: 12560–12568

    Article  CAS  Google Scholar 

  11. Kang H, Shamim M, Yin X, Adluru E, Fukuda T, Yokomizo S, Chang H, Park SH, Cui Y, Moy AJ, Kashiwagi S, Henary M, Choi HS. Adv Mater, 2022, 34: 2106500

    Article  CAS  Google Scholar 

  12. Chen HY. Sci China Chem, 2020, 63: 564–588

    Article  CAS  Google Scholar 

  13. Wang K, Jiang L, Zhang F, Wei Y, Wang K, Wang H, Qi Z, Liu S. Anal Chem, 2018, 90: 14056–14062

    Article  CAS  PubMed  Google Scholar 

  14. Lima C, Muhamadali H, Xu Y, Kansiz M, Goodacre R. Anal Chem, 2021, 93: 3082–3088

    Article  CAS  PubMed  Google Scholar 

  15. Xiong M, Yang Z, Lake RJ, Li J, Hong S, Fan H, Zhang X, Lu Y. Angew Chem IntEd, 2020, 59: 1891–1896

    Article  CAS  Google Scholar 

  16. Gavins GC, Gröger K, Bartoschek MD, Wolf P, Beck-Sickinger AG, Bultmann S, Seitz O. Nat Chem, 2021, 13: 15–23

    Article  CAS  PubMed  Google Scholar 

  17. Xiao H, Zhang W, Li P, Zhang W, Wang X, Tang B. Angew Chem Int Ed, 2020, 59: 4216–4230

    Article  CAS  Google Scholar 

  18. Nguyen LBT, Leong YX, Koh CSL, Leong SX, Boong SK, Sim HYF, Phan-Quang GC, Phang IY, Ling XY. Angew Chem IntEd, 2022, 61: e202207447

    CAS  Google Scholar 

  19. Zhou W, Ni X, Xie C, Fan Q, Liu D. Sci China Chem, 2021, 65: 48–67

    Article  Google Scholar 

  20. Fu BB, Tian XD, Song JJ, Wen BY, Zhang YJ, Fang PP, Li JF. Anal Chem, 2022, 94: 9578–9585

    Article  CAS  PubMed  Google Scholar 

  21. Zhao Y, Xu B, Tong L, Zhang J. Sci China Chem, 2021, 65: 269–283

    Article  Google Scholar 

  22. Liu Z, Tian Y. Sci China Chem, 2021, 64: 915–931

    Article  CAS  Google Scholar 

  23. Chen ZC, Xu HB, Chen HY, Zhu SC, Huang WF, He Y, Hafez ME, Qian RC, Li DW. Anal Chem, 2022, 94: 14280–14289

    Article  CAS  PubMed  Google Scholar 

  24. Lin S, Cheng Z, Li Q, Wang R, Yu F. ACS Sens, 2021, 6: 3912–3932

    Article  CAS  PubMed  Google Scholar 

  25. Avni A, Joshi A, Walimbe A, Pattanashetty SG, Mukhopadhyay S. Nat Commun, 2022, 13: 4378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zhang Y, Radjenovic PM, Zhou X, Zhang H, Yao J, Li J. Adv Mater, 2021, 33: 2005900

    Article  CAS  Google Scholar 

  27. Mueller NS, Pfitzner E, Okamura Y, Gordeev G, Kusch P, Lange H, Heberle J, Schulz F, Reich S. ACSNano, 2021, 15: 5523–5533

    CAS  Google Scholar 

  28. Wang X, Huang SC, Hu S, Yan S, Ren B. NatRevPhys, 2020, 2: 253–271

    Google Scholar 

  29. Wang J, Li XL, Chen HY, Xu JJ. Anal Chem, 2020, 92: 15647–15654

    Article  CAS  PubMed  Google Scholar 

  30. Wang L, Hasanzadeh Kafshgari M, Meunier M. Adv Funct Mater, 2020, 30: 2005400

    Article  CAS  Google Scholar 

  31. Qi C, Fu LH, Xu H, Wang TF, Lin J, Huang P. Sci China Chem, 2019, 62: 162–188

    Article  CAS  Google Scholar 

  32. Lin S, Ze H, Zhang X, Zhang Y, Song J, Zhang H, Zhong H, Yang Z, Yang C, Li J, Zhu Z. Angew Chem Int Ed, 2022, 61

  33. Liu G, Zhao J, Yan M, Zhu S, Dou W, Sun J, Yang X. Sci China Chem, 2020, 63: 554–560

    Article  CAS  Google Scholar 

  34. Witwer KW, Wolfram J. Nat Rev Mater, 2021, 6: 103–106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Lin JS, Tian XD, Li G, Zhang FL, Wang Y, Li JF. Chem Soc Rev, 2022, 51: 9445–9468

    Article  CAS  PubMed  Google Scholar 

  36. Zhao Q, Hilal H, Kim J, Park W, Haddadnezhad MN, Lee J, Park W, Lee JW, Lee S, Jung I, Park S. J Am Chem Soc, 2022, 144: 13285–13293

    Article  CAS  PubMed  Google Scholar 

  37. Liu ZC, Zhu Y, Zhang LM, Jiang WP, Liu YW, Tang QW, Cai XQ, Li J, Wang LH, Tao CL, Yin XZ, Li XW, Hou SG, Jiang DW, Liu K, Zhou X, Zhang HJ, Liu M, Fan CH, Tian Y. Sci China Chem, 2023, 66: 324–366

    Article  CAS  PubMed  Google Scholar 

  38. Sau TK, Murphy CJ. Langmuir, 2004, 20: 6414–6420

    Article  CAS  PubMed  Google Scholar 

  39. Nikoobakht B, El-Sayed MA. Chem Mater, 2003, 15: 1957–1962

    Article  CAS  Google Scholar 

  40. Liu Y, Li M, Chen G. J Mater Chem A, 2013, 1: 930–937

    Article  CAS  Google Scholar 

  41. Xie J, Lee JY, Wang DIC. Chem Mater, 2007, 19: 2823–2830

    Article  CAS  Google Scholar 

  42. Xie J, Zhang Q, Lee JY, Wang DIC. ACS Nano, 2008, 2: 2473–2480

    Article  CAS  PubMed  Google Scholar 

  43. Pan Y, Zhu Y, Xu C, Pan C, Shi Y, Zou J, Li Y, Hu X, Zhou B, Zhao C, Gao Q, Zhang J, Wu A, Chen X, Li J. ACS Nano, 2022, 16: 19038–19052

    Article  CAS  PubMed  Google Scholar 

  44. Veskoukis AS, Tsatsakis AM, Kouretas D. Cell Stress Chaperones, 2012, 17: 11–21

    Article  CAS  PubMed  Google Scholar 

  45. Zhao Y, Gu X, Ma H, He X, Liu M, Ding Y. J Phys Chem C, 2011, 115: 12797–12802

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (22234005, 21974070, 22222407, 22176099), the Natural Science Foundation of Jiangsu Province (BK20192008) and the State Key Laboratory of Analytical Chemistry for Life Science (SKLACLS2220).

Author information

Authors and Affiliations

  1. Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, China

    Min Zhang, Zijun Li, Mengyang Zhang, Shiying Xu, Zhaoyin Wang & Zhihui Dai

  2. Center for Analysis and Testing, Nanjing Normal University, Nanjing, 210023, China

    Hang Heng

  3. School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing, 211816, China

    Zhihui Dai

Authors
  1. Min Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zijun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mengyang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hang Heng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shiying Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhaoyin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhihui Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Zhaoyin Wang or Zhihui Dai.

Ethics declarations

The authors declare no conflict of interest.

Additional information

Supporting information

The supporting information is available online at chem.scichina.com and link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

Supporting Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, M., Li, Z., Zhang, M. et al. Raman imaging analysis of intracellular biothiols independent of the aggregation of sensing substrates. Sci. China Chem. 66, 2416–2424 (2023). https://doi.org/10.1007/s11426-023-1621-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11426-023-1621-3

Search

Navigation