Microchimica Acta

, Volume 184, Issue 5, pp 1315–1324 | Cite as

On−off−on gold nanocluster-based near infrared fluorescent probe for recognition of Cu(II) and vitamin C

Original Paper


The authors described gold nanoclusters (AuNCs) for use on an “on − off − on” NIR fluorescent probe for the determination of citrate and Cu(II) ion. The AuNCs were prepared by a microwave-assisted method using BSA as both the stabilizing and reducing agent. The resulting BSA-capped AuNCs display NIR fluorescence peaking at 680 nm under 500 nm excitation, a quantum yield of ~6.0%, an average size of 2.8 ± 0.5 nm, water-dispersibility, stability and biocompatibility. The on−off probe for Cu(II) is based on the interaction between Cu(II) and BSA which causes the fluorescence of the BSA−AuNCs to be quenched. The quenched fluorescence is recovered on addition of vitamin C (VC), obviously due to complexation of Cu(II) by citrate. The probe was employed to image Cu(II) and citrate in HeLa cells and in aqueous solutions. The method works in the 20 nM to 0.1 mM concentration range for Cu(II), and in the 8 nM to 120 μM concentration range for VC.

Graphical abstract

Schematic presentation of the gold nanocluster based probe whose fluorescence is quenched by Cu(II) ions and then restored by addition of vitamin C. This is demonstrated for both aqueous solutions and living cells.


Nanoprobe On-off-on probe Fluorescence Near-infrared Metal nanoclusters Imaging HeLa cells Microscopy Cells 



This work was supported by the National Natural Science Foundation of China (No. 51503085), the Natural Science Foundation of Jiangsu Province, China (No. BK20140157), open project of state key laboratory of supramolecular structure and materials (sklssm201621), Provincial Institution Promotion Plan (2015024-3), Public Health Research Center at Jiangnan University (No.JUPH201506), 2015 postgraduate practice innovation project of ordinary college in Jiangsu (SJLX15_0552).

Compliance with ethical standards

The authors have no competing interests.

Supplementary material

604_2017_2111_MOESM1_ESM.doc (2 mb)
ESM 1 (DOC 2.03 mb)


  1. 1.
    Guan WJ, Zhou WJ, Lu J, Lu C (2015) Luminescent films for chemo- and biosensing. Chem Soc Rev 44:6981–7009CrossRefGoogle Scholar
  2. 2.
    Han JS, Zhang X, Zhou YB, Ning Y, Wu J, Liang S, Sun HC, Zhang H, Yang B (2012) Fabrication of CdTe nanoparticles-based superparticles for an improved detection of Cu2+ and Ag+. J Mater Chem 22:2679–2686CrossRefGoogle Scholar
  3. 3.
    Yang XD, Shen BW, Jiang YN, Zhao ZX, Wang CX, Ma C, Yang B, Lin Q (2013) A novel fluorescent polymer brushes film as a device for ultrasensitive detection of TNT. J Mater Chem A 1:1201–1206CrossRefGoogle Scholar
  4. 4.
    Ma Q, Su XG (2011) Recent advances and applications in QDs-based sensors. Analyst 136:4883–4893CrossRefGoogle Scholar
  5. 5.
    Jiang YN, Yang XD, Ma C, Wang CX, Li H, Dong FX, Zhai XM, Yu K, Lin Q, Yang B (2010) Photoluminescent smart hydrogels with reversible and linear Thermoresponses. Small 6:2673–2677CrossRefGoogle Scholar
  6. 6.
    Wang CX, Xu ZZ, Cheng H, Lin HH, Humphrey MG, Zhang C (2015) A hydrothermal route to water-stable luminescent carbon dots as nanosensors for pH and temperature. Carbon 82:87–95CrossRefGoogle Scholar
  7. 7.
    Wang CX, Cheng H, Huang YJ, Xu ZZ, Lin HH, Zhang C (2015) Facile sonochemical synthesis of pH-responsive copper nanoclusters for selective and sensitive detection of Pb2+ in living cells. Analyst 140:5634–5639CrossRefGoogle Scholar
  8. 8.
    Guo ZQ, Park SK, Yoon JY, Shin I (2014) Recent progress in the development of near-infrared fluorescent probes for bioimaging applications. Chem Soc Rev 43:16–29CrossRefGoogle Scholar
  9. 9.
    Wang CX, Wang Y, Xu L, Zhang D, Liu MX, Li XW, Sun HC, Lin Q, Yang B (2012) Facile aqueous-phase synthesis of biocompatible and fluorescent Ag2S nanoclusters for bioimaging: tunable photoluminescence from red to near infrared. Small 8:3137–3142CrossRefGoogle Scholar
  10. 10.
    Du JJ, Yu CM, Pan DC, Li JM, Chen W, Yan M, Segura T, Lu YF (2010) Quantum-dot-decorated robust Transductable bioluminescent Nanocapsules. J Am Chem Soc 132:12780–12781CrossRefGoogle Scholar
  11. 11.
    Wang CX, Xu L, Xu XW, Cheng H, Sun HC, Lin Q, Zhang C (2014) Near infrared Ag/Au alloy nanoclusters: tunable photoluminescence and cellular imaging. J Colloid Interface Sci 416:274–279CrossRefGoogle Scholar
  12. 12.
    Goswami N, Giri A, Kar S, Bootharaju MS, John R, Xavier PL, Pradeep T, Pal SK (2012) Protein-directed synthesis of NIR-emitting, tunable HgS quantum dots and their applications in metal-ion sensing. Small 8:3175–3184CrossRefGoogle Scholar
  13. 13.
    Xia YS, Song L, Zhu CQ (2011) Turn-on and near-infrared fluorescent sensing for 2,4,6-trinitrotoluene based on hybrid (gold nanorod)-(quantum dots) assembly. Anal Chem 83:1401–1407CrossRefGoogle Scholar
  14. 14.
    Lu YZ, Chen W (2012) Sub-nanometre sized metal clusters: from synthetic challenges to the unique property discoveries. Chem Soc Rev 41:3594–3623CrossRefGoogle Scholar
  15. 15.
    Shang L, Dong SJ, Nienhaus GU (2011) Ultra-small fluorescent metal nanoclusters: synthesis and biological applications. Nano Today 6:401–418CrossRefGoogle Scholar
  16. 16.
    Zhang LB, Wang EK (2014) Metal nanoclusters: new fluorescent probes for sensors and bioimaging. Nano Today 9:132–157CrossRefGoogle Scholar
  17. 17.
    Wang CX, Wang Y, Xu Y, Shi XD, Li XW, Xu XW, Sun HC, Yang B, Lin Q (2013) A galvanic replacement route to prepare strongly fluorescent and highly stable gold Nanodots for cellular imaging. Small 9:413–420CrossRefGoogle Scholar
  18. 18.
    Wang CX, Cheng H, Sun YQ, Lin Q, Zhang C (2015) Rapid sonochemical synthesis of luminescent and paramagnetic copper nanoclusters for bimodal bioimaging. Chem NanoMat 1:27–31Google Scholar
  19. 19.
    Li G, Jin RC (2013) Atomically precise gold nanoclusters as new model catalysts. Acc Chem Res 46:1749–1758CrossRefGoogle Scholar
  20. 20.
    Zheng J, Zhou C, Yu MX, Liu JB (2012) Different sized luminescent gold nanoparticles. Nanoscale 4:4073–4083CrossRefGoogle Scholar
  21. 21.
    Shang YC, Huang CC, Chen WY, Chen PC, Chang HT (2012) Fluorescent gold and silver nanoclusters for analysis of biopolymers and cell imaging. J Mater Chem 22:12972–12982CrossRefGoogle Scholar
  22. 22.
    Chen LY, Wang CW, Yuan ZQ, Chang HT (2015) Fluorescent gold nanoclusters: recent advances in sensing and imaging. Anal Chem 87:216–229CrossRefGoogle Scholar
  23. 23.
    Zheng J, Petty JT, Dickson RM (2003) High quantum yield blue emission from water-soluble Au8 Nanodots. J Am Chem Soc 125:7780–7781CrossRefGoogle Scholar
  24. 24.
    Chen Y, Zhou HP, Wang Y, Li WY, Chen J, Lin Q, Yu C (2013) Substrate hydrolysis triggered formation of fluorescent gold nanoclusters – a new platform for the sensing of enzyme activity. Chem Commun 49:9821–9823CrossRefGoogle Scholar
  25. 25.
    Bilecka I, Niederberger M (2010) Microwave chemistry for inorganic nanomaterials synthesis. Nanoscale 2:1358–1374CrossRefGoogle Scholar
  26. 26.
    Hsu NY, Lin YW (2016) Microwave-assisted synthesis of bovine serum albumin–gold nanoclusters and their fluorescence-quenched sensing of Hg2+ ions. New J Chem 40:1155–1161CrossRefGoogle Scholar
  27. 27.
    Raut S, Rich R, Fudala R, Butler S, Kokate R, Gryczynski Z, Luchowskic R, Gryczynski I (2014) Resonance energy transfer between fluorescent BSA protected Au nanoclusters and organic fluorophores. Nanoscale 6:385–391CrossRefGoogle Scholar
  28. 28.
    Gu Y, Li N, Gao M, Wang Z, Xiao D, Li Y, Jia H, He H (2015) Microwave-assisted synthesis of BSA-modified silver nanoparticles as a selective fluorescent probe for detection and cellular imaging of cadmium(II). Microchim Acta 182:1255–1261CrossRefGoogle Scholar
  29. 29.
    Chen Y, Wang Y, Wang CX, Li WY, Zhou HP, Jiao HP, Lin Q, Yu C (2013) Papain-directed synthesis of luminescent gold nanoclusters and the sensitive detection of Cu2+. J Colloid Interface Sci 396:63–68CrossRefGoogle Scholar
  30. 30.
    Chen Y, Li WY, Wang Y, Yang XD, Chen J, Jiang YN, Yu C, Lin Q (2014) Cysteine-directed fluorescent gold nanoclusters for the sensing of pyrophosphate and alkaline phosphatase. J Mater Chem C 2:4080–4085CrossRefGoogle Scholar
  31. 31.
    Yang S, Jiang Z, Chen Z, Tong L, Lu J, Wang J (2015) Bovine serum albumin-stabilized gold nanoclusters as a fluorescent probe for determination of ferrous ion in cerebrospinal fluids via the Fenton reaction. Microchim Acta 182:1911–1916CrossRefGoogle Scholar
  32. 32.
    Xu S, Yang H, Zhao K, Li J, Mei L, Xie Y, Deng A (2015) Preparation of orange-red fluorescent gold nanoclusters using denatured casein as a reductant and stabilizing agent, and their application to imaging of HeLa cells and for the quantitation of mercury (II). Microchim Acta 182:2577–2584CrossRefGoogle Scholar
  33. 33.
    Shang L, Stockmar F, Azadfar N, Nienhaus GU (2013) Intracellular thermometry by using fluorescent gold nanoclusters. Angew Chem Int Ed 52:11154–11157CrossRefGoogle Scholar
  34. 34.
    Wang CX, Lin HH, Xu ZZ, Huang YJ, Humphrey MG, Zhang C (2016) Tunable carbon-dot-based dual-emission fluorescent nanohybrids for ratiometric optical thermometry in living cells. ACS Appl Mater Interfaces 8:6621–6628CrossRefGoogle Scholar
  35. 35.
    Xu ZZ, Wang CX, Jiang KL, Lin HH, Huang YJ, Zhang C (2015) Microwave-assisted rapid synthesis of amphibious yellow fluorescent carbon dots as a colorimetric nanosensor for Cr(VI). Part Part Syst Charact 32:1058–1062CrossRefGoogle Scholar
  36. 36.
    Liu Y, Tian GF, He XW, Li WY, Zhang YK (2016) Microwave-assisted one-step rapid synthesis of near-infrared gold nanoclusters for NIRF/CT dual-modal bioimaging. J Mater Chem B 4:1276–1283CrossRefGoogle Scholar
  37. 37.
    Yan L, Cai YQ, Zheng BZ, Yuan HY, Guo Y, Xiao D, Choi MMF (2012) Microwave-assisted synthesis of BSA-stabilized and HSA-protected gold nanoclusters with red emission. J Mater Chem 22:1000–1005CrossRefGoogle Scholar
  38. 38.
    Raut S, Chi R, Rich R, Shumilov D, Gryczynski Z, Gryczynski I (2013) Polarization properties of fluorescent BSA protected Au25 nanoclusters. Nanoscale 5:3441–3446CrossRefGoogle Scholar
  39. 39.
    Wang CX, Cheng H, Sun YQ, Xu ZZ, Lin HH, Lin Q, Zhang C (2015) Nanoclusters prepared from a silver/gold alloy as a fluorescent probe for selective and sensitive determination of lead(II). Microchim Acta 182:695–701CrossRefGoogle Scholar
  40. 40.
    Li J, Wu J, Zhang X, Liu Y, Zhou D, Sun HZ, Zhang H, Yang B (2011) Controllable synthesis of stable urchin-like gold nanoparticles using hydroquinone to tune the reactivity of gold chloride. J Phys Chem C 115:3630–3637CrossRefGoogle Scholar
  41. 41.
    Udayabhaskararao T, Sun Y, Goswami N, Samir KP, Balasubramanian K, Pradeep T (2012) Ag7Au6: a 13-atom alloy quantum cluster. Angew Chem Int Ed 51:2155–2159CrossRefGoogle Scholar
  42. 42.
    Qu SN, Zhou D, Li D, Ji WY, Jing PT, Han D, Liu L, Zeng HB, Shen DZ (2016) Toward efficient Orange emissive carbon Nanodots through conjugated sp2-domain controlling and surface charges engineering. Adv Mater 28:3516–3521CrossRefGoogle Scholar
  43. 43.
    Zhou J, Yang Y, Zhang CY (2013) A low-temperature solid-phase method to synthesize highly fluorescent carbon nitride dots with tunable emission. Chem Commun 49:8605–8607CrossRefGoogle Scholar
  44. 44.
    Chen PC, Chiang CK, Chang HT (2013) Synthesis of fluorescent BSA–Au NCs for the detection of Hg2+ ions. J Nanopart Res 15:1336–1345CrossRefGoogle Scholar
  45. 45.
    Ding H, Yu SB, Wei JS, Xiong HM (2016) Full-color light-emitting carbon dots with a surface-state-controlled luminescence mechanism. ACS Nano 10:484–491CrossRefGoogle Scholar
  46. 46.
    Hu DH, Sheng ZH, Gong P, Zhang PF, Cai LT (2010) Highly selective fluorescent sensors for Hg2+ based on bovine serum albumin-capped gold nanoclusters. Analyst 135:1411–1416CrossRefGoogle Scholar
  47. 47.
    Mathew A, Sajanlal PR, Pradeep T (2011) A fifteen atom silver cluster confined in bovine serum albumin. J Mater Chem 21:11205–11212CrossRefGoogle Scholar
  48. 48.
    Xie JP, Zheng YG, Ying JY (2009) Protein-directed synthesis of highly fluorescent gold nanoclusters. J Am Chem Soc 131:888–889CrossRefGoogle Scholar
  49. 49.
    Richards C, Choi S, Hsiang JC, Antoku Y, Vosch T, Bongiorno A, Tzeng YL, Dickson RM (2008) Oligonucleotide-stabilized Ag Nanocluster fluorophores. J Am Chem Soc 130:5038–5039CrossRefGoogle Scholar
  50. 50.
    Shang L, Nienhaus GU (2012) Gold nanoclusters as novel optical probes for in vitro and in vivo fluorescence imaging. Biophys Rev 4:313–322CrossRefGoogle Scholar
  51. 51.
    Chen YN, Chen PC, Wang CX, Lin YS, Ou CM, Ho LC, Chang HT (2014) One-pot synthesis of fluorescent BSA–Ce/Au nanoclusters as ratiometric pH probes. Chem Commun 50:8571–8574CrossRefGoogle Scholar
  52. 52.
    Unnikrishnan B, Wei SC, Chiu WJ, Cang JS, Hsu PH, Huang CC (2014) Nitrite ion-induced fluorescence quenching of luminescent BSA-Au25 nanoclusters: mechanism and application. Analyst 139:2221–2228CrossRefGoogle Scholar
  53. 53.
    Cheng H, Wang CX, Xu ZZ, Lin HH, Zhang C (2015) Gold nanoparticle-enhanced near infrared fluorescent nanocomposites for targeted bio-imaging. RSC Adv 5:20–26CrossRefGoogle Scholar
  54. 54.
    Lovrić J, Bazzi HS, Cuie Y, Fortin GRA, Winnik FM, Maysinger D (2005) Differences in subcellular distribution and toxicity of green and red emitting CdTe quantum dots. J Mol Med 83:377–385CrossRefGoogle Scholar
  55. 55.
    Goswami N, Giri A, Bootharaju MS, Xavier PL, Pradeep T, Pal SK (2011) Copper quantum clusters in protein matrix: potential sensor of Pb2+ ion. Anal Chem 83:9676–9680CrossRefGoogle Scholar
  56. 56.
    Adhikari A, Banerjee A (2010) Facile synthesis of water-soluble fluorescent silver nanoclusters and HgII sensing. Chem Mater 22:4364–4371CrossRefGoogle Scholar
  57. 57.
    Xie JP, Zheng YG, Ying JY (2010) Highly selective and ultrasensitive detection of Hg2+ based on fluorescence quenching of Au nanoclusters by Hg2 + −Au + interactions. Chem Commun 46:961–963CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2017

Authors and Affiliations

  1. 1.China-Australia Joint Research Centre for Functional Molecular Materials, School of Chemical & Material EngineeringJiangnan UniversityWuxiPeople’s Republic of China
  2. 2.Institute of New Energy TechnologyNingbo Institute of Industrial Technology, Chinese Academy of SciencesNingboPeople’s Republic of China
  3. 3.School of Chemical Science and EngineeringTongji UniversityShanghaiPeople’s Republic of China

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