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A nanoprobe for ratiometric imaging of glutathione in living cells based on the use of a nanocomposite prepared from dual-emission carbon dots and manganese dioxide nanosheets

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Abstract

A ratiometric fluorescence assay for glutathione (GSH) was developed. The novel assay is based on a nanoprobe composed of manganese dioxide nanosheets (MnO2 NS) and dual-emission carbon dots (de-CDs) with intrinsic GSH-response property. After construction of the nanoprobe, two emission peaks of de-CDs were suppressed to varying degrees by MnO2 NS. The suppression was relieved and the two emission peaks recovered proportionally when MnO2 NS was decomposed by GSH, thus realizing the ratiometric assay for micromolar GSH. The intrinsic responsiveness of de-CDs to millimolar GSH broadens the analytical range of the nanoprobe. An appropriate precursor, calcon-carboxylic acid, was screened out to synthesize de-CDs via one-step hydrothermal treatment. The de-CD@MnO2 NS nanoprobe can measure GSH concentrations through the fluorescence intensity ratio between 435 and 516 nm excited at 365 nm. The range of response was from 1 μM to 10 mM and the detection limit reached 0.6 μM (3σ criterion). Benefiting from its good biocompatibility, the proposed nanoprobe has excellent applicability for intracellular GSH imaging.

Graphical abstract

Schematic representation of glutathione (GSH) ratiometric detection. The nanoprobe is prepared from dual-emission carbon dots (de-CDs) and manganese dioxide nanosheets (MnO2 NS). GSH removes quenching effect by decomposing MnO2 NS and induces intrinsic response of de-CDs, which realizes ratiometric detection.

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References

  1. Ren X, Zou L, Zhang X, Branco V, Wang J, Carvalho C, Holmgren A, Lu J (2017) Redox signaling mediated by thioredoxin and glutathione systems in the central nervous system. Antioxid Redox Sign 27:13

    Google Scholar 

  2. Calabrese G, Morgan B, Riemer J (2017) Mitochondrial glutathione: regulation and functions. Antioxid. Redox Sign 27:15

    Google Scholar 

  3. Sedlak TW, Paul BD, Parker GM, Hester LD, Snowman AM, Taniguchi Y, Kamiya A, Snyder SH, Sawa A (2019) The glutathione cycle shapes synaptic glutamate activity. P Natl Acad Sci U S A 116:2701–2706

    Article  CAS  Google Scholar 

  4. Benhar M, Shytaj IL, Stamler JS, Savarino A (2016) Dual targeting of the thioredoxin and glutathione systems in cancer and HIV. J Clin Invest 126:1630–1639

    Article  Google Scholar 

  5. Géhla Z, Bakondi E, Resch MD, Hegedűs C, Kovács K, Lakatos P, Szabó A, Nagy Z, Virág L (2016) Diabetes-induced oxidative stress in the vitreous humor. Redox Biol 9:100–103

    Article  Google Scholar 

  6. Gorrini C, Mak TW (2019) Glutathione metabolism: an Achilles’ heel of ARID1A-deficient tumors. Cancer Cell 35:161–163

    Article  CAS  Google Scholar 

  7. Peng HP, Jian ML, Huang ZN, Wang WJ, Deng HH, Wu WH, Liu AL, Xia XH, Chen W (2018) Facile electrochemiluminescence sensing platform based on high-quantum-yield gold nanocluster probe for ultrasensitive glutathione detection. Biosens Bioelectron 105:71–76

    Article  CAS  Google Scholar 

  8. Shi W, Song B, Shi W, Qin X, Liu Z, Tan M, Wang L, Song F, Yuan J (2018) Bimodal phosphorescence–magnetic resonance imaging nanoprobes for glutathione based on MnO2 nanosheet–Ru(II) complex nanoarchitecture. ACS Appl Mater Interfaces 10:27681–27691

    Article  CAS  Google Scholar 

  9. Zhang Y, Zhang W, Chen K, Yang Q, Hu N, Suo Y, Wang J (2018) Highly sensitive and selective colorimetric detection of glutathione via enhanced Fenton-like reaction of magnetic metal organic framework. Sensor Actuat B – Chem 262:95–101

    Article  CAS  Google Scholar 

  10. Hu X, Liu X, Zhang X, Cao H, Huang Y (2019) MnO2 nanowires tuning of photoluminescence of alloy Cu/Ag NCs and thiamine enables a ratiometric fluorescent sensing of glutathione. Sensor Actuat B – Chem 286:476–482

    Article  CAS  Google Scholar 

  11. Tang M, Zhu B, Wang Y, Wu H, Chai F, Qu F, Su Z (2019) Nitrogen- and sulfur-doped carbon dots as peroxidase mimetics: colorimetric determination of hydrogen peroxide and glutathione, and fluorimetric determination of lead(II). Microchim Acta 186:604

    Article  Google Scholar 

  12. Tang X, Zeng X, Liu H, Yang Y, Zhou H, Cai H (2019) A nanohybrid composed of MoS2 quantum dots and MnO2 nanosheets with dual-emission and peroxidase mimicking properties for use in ratiometric fluorometric detection and cellular imaging of glutathione. Microchim Acta 186:572

    Article  Google Scholar 

  13. Wu P, Hou X, Xu JJ, Chen HY (2016) Ratiometric fluorescence electrochemiluminescence and photoelectrochemical chemo/biosensing based on semiconductor quantum dots. Nanoscale 8:8427–8442

    Article  CAS  Google Scholar 

  14. Huang X, Song J, Yung BC, Huang X, Xiong Y, Chen X (2018) Ratiometric optical nanoprobes enable accurate molecular detection and imaging. Chem Soc Rev 47:2873–2920

    Article  CAS  Google Scholar 

  15. Gui R, Jin H, Bu X, Fu Y, Wang Z, Liu Q (2019) Recent advances in dual-emission ratiometric fluorescence probes for chemo/biosensing and bioimaging of biomarkers. Coordin Chem Rev 383:82–103

    Article  CAS  Google Scholar 

  16. Ma Z, Wu T, Li P, Liu M, Huang S, Li H, Zhang Y, Yao S (2019) A dual (colorimetric and fluorometric) detection scheme for glutathione and silver (I) based on the oxidase mimicking activity of MnO2 nanosheets. Microchim Acta 186:498

    Article  Google Scholar 

  17. Yin C, Tang Y, Li X, Yang Z, Li J, Li X, Huang W, Fan QA (2018) Single composition architecture-based nanoprobe for ratiometric photoacoustic imaging of glutathione (GSH) in living mice. Small 14:1703400

    Article  Google Scholar 

  18. Qi S, Liu W, Zhang P, Wu J, Zhang H, Ren H, Ge J, Wang P (2018) A colorimetric and probe for highly selective detection of glutathione in the mitochondria of living cells. Sensor Actuat B - Chem 270:459–465

    Article  CAS  Google Scholar 

  19. Zheng J, Wu Y, Xing D, Zhang T (2019) Synchronous detection of glutathione/hydrogen peroxide for monitoring redox status in vivo with a ratiometric upconverting nanoprobe. Nano Res 12:931–938

    Article  CAS  Google Scholar 

  20. Zhi B, Cui Y, Wang S, Frank BP, Williams DN, Brown RP, Melby ES, Hamers RJ, Rosenzweig Z, Fairbrother DH, Orr G, Haynes CL (2018) Malic acid carbon dots: from super-resolution live-cell imaging to highly efficient separation. ACS Nano 12:5741–5752

    Article  CAS  Google Scholar 

  21. Hassan M, Gomes VG, Dehghani A, Ardekani SM (2018) Engineering carbon quantum dots for photomediated theranostics. Nano Res 11:1–41

    Article  Google Scholar 

  22. Du J, Xu N, Fan J, Sun W, Peng X (2019) Carbon dots for in vivo bioimaging and theranostics. Small 15:1805087

    Article  Google Scholar 

  23. Yan F, Sun Z, Zhang H, Sun X, Jiang Y, Bai Z (2019) The fluorescence mechanism of carbon dots, and methods for tuning their emission color: a review. Microchim Acta 186:583

    Article  Google Scholar 

  24. He D, Yang X, HeX MK, He X, Zou Z (2015) A sensitive turn-on fluorescent probe for intracellular imaging of glutathione using single-layer MnO2 nanosheet-quenched fluorescent carbon quantum dots. Chem Commun 51:14764–14767

    Article  CAS  Google Scholar 

  25. Wang Y, Jiang K, Zhu J, Zhang L, Lin H (2015) A FRET-based carbon dot–MnO2 nanosheet architecture for glutathione sensing in human whole blood samples. Chem Commun 51:12748–12751

    Article  CAS  Google Scholar 

  26. Xu Y, Chen X, Chai R, Xing C, Li H, Yin XB (2016) A magnetic/fluorometric bimodal sensor based on a carbon dots–MnO2 platform for glutathione detection. Nanoscale 8:13414–13421

    Article  CAS  Google Scholar 

  27. Cui Y, Liu R, Ye F, Zhao S (2019) Single-excitation dual-emission biomass quantum dots: preparation and application for ratiometric fluorescence imaging of coenzyme A in living cells. Nanoscale 11:9270–9275

    Article  CAS  Google Scholar 

  28. Chen L, Park SJ, Wu D, Kim HM, Yoon J (2019) A two-photon fluorescent probe for colorimetric and ratiometric monitoring of mercury in live cells and tissues. Chem Commun 55:1766–1769

    Article  CAS  Google Scholar 

  29. Wu S, Min H, Shi W, Cheng P (2019) Multicenter metal–organic framework-based ratiometric fluorescent sensors. Adv Mater 2019:e1805871. https://doi.org/10.1002/adma.201805871

    Article  CAS  Google Scholar 

  30. Fan H, Zhao Z, Yan G, Zhang X, Yang C, Meng H, Chen Z, Liu H, Tan W (2015) A smart DNAzyme–MnO2 nanosystem for efficient gene silencing. Angew Chem Int Edit 54:4801–4805

    Article  CAS  Google Scholar 

  31. Zhu Z, Zhai Y, Li Z, Zhu P, Mao S, Zhu C, Du D, Belfiore LA, Tang J, Lin Y (2019) Red carbon dots: optical property regulations and applications. Mater Today 30:52–79

    Article  CAS  Google Scholar 

  32. Shangguan J, He D, He X, Wang K, Xu F, Liu J, Tang J, Yang X, Huang J (2016) Label-free carbon-dots-based ratiometric fluorescence pH nanoprobes for intracellular pH sensing. Anal Chem 88:7837–7843

    Article  CAS  Google Scholar 

  33. Song W, DuanW LY, Ye Z, Chen Y, Chen H, Qi S, Wu J, Liu D, Xiao L, Ren C, Chen X (2017) Ratiometric detection of intracellular lysine and pH with one-pot synthesized dual emissive carbon dots. Anal Chem 89:13626–13633

    Article  CAS  Google Scholar 

  34. Dong Y, Shao J, Chen C, Li H, Wang R, Chi Y, Lin X, Chen G (2012) Blue luminescent graphene quantum dots and graphene oxide prepared by tuning the carbonization degree of citric acid. Carbon 50:4738–4743

    Article  CAS  Google Scholar 

  35. Chen J, Meng H, Tian Y, Yang R, Du D, Li Z, Qu L, Lin Y (2019) Recent advances in functionalized MnO2 nanosheets for biosensing and biomedicine applications. Nanoscale Horiz 4:321–338

    Article  CAS  Google Scholar 

  36. Zhai W, Wang C, Yu P, Wang Y, Mao L (2014) Single-layer MnO2 nanosheets suppressed fluorescence of 7-hydroxycoumarin: mechanistic study and application for sensitive sensing of ascorbic acid in vivo. Anal Chem 86:12206–12213

    Article  CAS  Google Scholar 

  37. Deng R, Xie X, Vendrell M, Chang YT, Liu X (2011) Intracellular glutathione detection using MnO2-nanosheet-modified upconversion nanoparticles. J Am Chem Soc 133:20168–20171

    Article  CAS  Google Scholar 

  38. Peng C, Xing H, Fan X, Xue Y, Li J, Wang E (2019) Glutathione regulated inner filter effect of MnO2 nanosheets on boron nitride quantum dots for sensitive assay. Anal Chem 91:5762–5767

    Article  CAS  Google Scholar 

  39. Cai Q Y, Li J, Ge J, Zhang L, Hu Y L, Li Z H, Qu L B (2015) A rapid fluorescence “switch-on” assay for glutathione detection by using carbon dots–MnO2 nanocomposites. 72: 31-36

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Funding

This study was funded by the National Natural Science Foundation of China (Grant No. 21804143 and No. 21576295), the Hunan Provincial Natural Science Foundation of China (2019JJ50759), and the Fundamental Research Funds for the Central Universities of Central South University (2017zzts175 and 2018zzts371).

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Correspondence to Yanjing Yang or Shian Zhong.

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Deng, Z., Li, X., Liu, H. et al. A nanoprobe for ratiometric imaging of glutathione in living cells based on the use of a nanocomposite prepared from dual-emission carbon dots and manganese dioxide nanosheets. Microchim Acta 187, 537 (2020). https://doi.org/10.1007/s00604-020-04495-1

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  • DOI: https://doi.org/10.1007/s00604-020-04495-1

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