Microchimica Acta

, Volume 178, Issue 1–2, pp 229–236 | Cite as

Silver–gold core-shell nanoparticles containing methylene blue as SERS labels for probing and imaging of live cells

  • Xi Guo
  • Zhouyi GuoEmail author
  • Ying Jin
  • Zhiming Liu
  • Wen Zhang
  • Deqiu Huang
Original Paper


We report on silver–gold core-shell nanostructures that contain Methylene Blue (MB) at the gold–silver interface. They can be used as reporter molecules in surface-enhanced Raman scattering (SERS) labels. The labels are stable and have strong SERS activity. TEM imaging revealed that these nanoparticles display bright and dark stripe structures. In addition, these labels can act as probes that can be detected and imaged through the specific Raman signatures of the reporters. We show that such SERS probes can identify cellular structures due to enhanced Raman spectra of intrinsic cellular molecules measured in the local optical fields of the core-shell nanostructures. They also provide structural information on the cellular environment as demonstrated for these nanoparticles as new SERS-active and biocompatible substrates for imaging of live cells.


The synthesis of MB embedded Ag/Au CS NPs ,and the results of these NPs were used in probing and imaging live cells as SERS labels


Surface-enhanced Raman scattering Ag/Au core-shell nanoparticles A549 cell SERS imaging 



This work was supported by the National Natural Science Foundation of China (Grant No.60778047), the Natural Science Foundation of Guangdong Province of China (Grant No. 9251063101000009), Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No.20114407110001),the cooperation project in industry, education and research of Guangdong province and Ministry of Education of P.R.China (Grant No. 2011A090200011) and the Key Science and Technology Project of Guangzhou City of China (Grant No. 2008Z1-D391).

Supplementary material

604_2012_829_MOESM1_ESM.doc (46 kb)
Table S1 (DOC 46 kb)


  1. 1.
    Cui Y, Ren B, Yao JL, Gu RA, Tian ZQ (2006) Synthesis of Ag core Au shell bimetallic nanoparticles for immunoassay based on surface-enhanced Raman spectroscopy. J Phys Chem B 110(9):4002–4006. doi: 10.1021/Jp056203x CrossRefGoogle Scholar
  2. 2.
    Docherty FT, Clark M, McNay G, Graham D, Smith WE (2004) Multiple labelled nanoparticles for bio detection. Faraday Discuss 126:281–288, discussion 303–211CrossRefGoogle Scholar
  3. 3.
    Zhang L, Shi HW, Wang C, Zhang KY (2011) Preparation of a nanocomposite film from poly(diallydimethyl ammonium chloride) and gold nanoparticles by in-situ electrochemical reduction, and its application to SERS spectroscopy and sensing of ascorbic acid. Microchim Acta 173(3–4):401–406. doi: 10.1007/s00604-011-0571-x CrossRefGoogle Scholar
  4. 4.
    Yeo BS, Schmid T, Zhang WH, Zenobi R (2007) Towards rapid nanoscale chemical analysis using tip-enhanced Raman spectroscopy with Ag-coated dielectric tips. Anal Bioanal Chem 387(8):2655–2662. doi: 10.1007/s00216-007-1165-7 CrossRefGoogle Scholar
  5. 5.
    Kumar GVP, Shruthi S, Vibha B, Reddy BAA, Kundu TK, Narayana C (2007) Hot spots in Ag core-Au shell nanoparticles potent for surface-enhanced Raman scattering studies of biomolecules. J Phys Chem C 111(11):4388–4392. doi: 10.1021/Jp068253n CrossRefGoogle Scholar
  6. 6.
    Xie W, Qiu P, Mao C (2011) Bio-imaging, detection and analysis by using nanostructures as SERS substrates. J Mater Chem 21(14):5190–5202CrossRefGoogle Scholar
  7. 7.
    Lee S, Kim S, Choo J, Shin SY, Lee YH, Choi HY, Ha SH, Kang KH, Oh CH (2007) Biological imaging of HEK293 cells expressing PLC gamma 1 using surface-enhanced Raman microscopy. Anal Chem 79(3):916–922. doi: 10.1021/Ac061246a CrossRefGoogle Scholar
  8. 8.
    Saunders AE, Popov I, Banin U (2006) Synthesis of hybrid CdS-Au colloidal nanostructures. J Phys Chem B 110(50):25421–25429. doi: 10.1021/Jp065594s CrossRefGoogle Scholar
  9. 9.
    Hu JW, Zhang Y, Li JF, Liu Z, Ren B, Sun SG, Tian ZQ, Lian T (2005) Synthesis of Au@Pd core-shell nanoparticles with controllable size and their application in surface-enhanced Raman spectroscopy. Chem Phys Lett 408(4–6):354–359. doi: 10.1016/j.cplett.2005.04.071 CrossRefGoogle Scholar
  10. 10.
    Kamata K, Lu Y, Xia YN (2003) Synthesis and characterization of monodispersed core-shell spherical colloids with movable cores. J Am Chem Soc 125. doi: 10.1021/Ja0292849
  11. 11.
    Ung T, Liz-Marzan LM, Mulvaney P (1999) Redox catalysis using Ag@SiO2 colloids. J Phys Chem B 103(32):6770–6773CrossRefGoogle Scholar
  12. 12.
    Luo ZH, Chen K, Lu DL, Han HY, Zou MQ (2011) Synthesis of p-aminothiophenol-embedded gold/silver core-shell nanostructures as novel SERS tags for biosensing applications. Microchim Acta 173(1–2):149–156. doi: 10.1007/s00604-010-0537-4 CrossRefGoogle Scholar
  13. 13.
    Sirimuthu NMS, Syme CD, Cooper JM (2010) Monitoring the uptake and redistribution of metal nanoparticles during cell culture using surface-enhanced Raman scattering spectroscopy. Anal Chem 82(17):7369–7373. doi: 10.1021/Ac101480t CrossRefGoogle Scholar
  14. 14.
    Kneipp J, Kneipp H, Wittig B, Kneipp K (2010) Novel optical nanosensors for probing and imaging live cells. Nanomedicine-Uk 6(2):214–226. doi: 10.1016/j.nano.2009.07.009 Google Scholar
  15. 15.
    Lucas L, Chen XK, Smith A, Korbelik M, Zeng H, Lee PWK, Hewitt KC (2009) Imaging EGFR distribution using surface enhanced Raman spectroscopy. Proc Soc Photo-Opt Ins 7192:–188. doi: 10.1117/12.808337
  16. 16.
    Luo Z, Fu T, Chen K, Han H, Zou M (2011) Synthesis of multi-branched gold nanoparticles by reduction of tetrachloroauric acid with Tris base, and their application to SERS and cellular imaging. Microchim Acta 175(1–2):55–61. doi: 10.1007/s00604-011-0649-5 Google Scholar
  17. 17.
    Doering WE, Piotti ME, Natan MJ, Freeman RG (2007) SERS as a foundation for nanoscale, optically detected biological labels. Adv Mater 19(20):3100–3108. doi: 10.1002/adma.200701984 CrossRefGoogle Scholar
  18. 18.
    Qian XM, Nie SM (2008) Single-molecule and single-nanoparticle SERS: from fundamental mechanisms to biomedical applications. Chem Soc Rev 37(5):912–920CrossRefGoogle Scholar
  19. 19.
    Kneipp J (2006) Nanosensors based on SERS for applications in living cells surface-enhanced Raman scattering. In: Kneipp K, Moskovits M, Kneipp H (eds) Topics in applied physics, vol 103. Springer, Berlin, pp 335–349. doi: 10.1007/3-540-33567-6_17 Google Scholar
  20. 20.
    Kneipp J, Kneipp H, Rice WL, Kneipp K (2005) Optical probes for biological applications based on surface-enhanced Raman scattering from indocyanine green on gold nanoparticles. Anal Chem 77(8):2381–2385. doi: 10.1021/ac050109v CrossRefGoogle Scholar
  21. 21.
    Kneipp J, Kneipp H, Rajadurai A, Redmond RW, Kneipp K (2009) Optical probing and imaging of live cells using SERS labels. J Raman Spectrosc 40(1):1–5. doi: 10.1002/jrs.2060 CrossRefGoogle Scholar
  22. 22.
    Lee PC, Meisel D (1982) Adsorption and surface-enhanced Raman of dyes on silver and gold sols. J Phys Chem 86(17):3391–3395. doi: 10.1021/j100214a025 CrossRefGoogle Scholar
  23. 23.
    Xiao G-N, Man S-Q (2007) Surface-enhanced Raman scattering of methylene blue adsorbed on cap-shaped silver nanoparticles. Chem Phys Lett 447(4–6):305–309. doi: 10.1016/j.cplett.2007.09.045 CrossRefGoogle Scholar
  24. 24.
    Mie G (1908) Beiträge zur Optik trüber Medien, speziell kolloidaler Metallösungen. Ann Phys 330(3):377–445. doi: 10.1002/andp.19083300302 CrossRefGoogle Scholar
  25. 25.
    Han XX, Xie Y, Zhao B, Ozaki Y (2010) Highly sensitive protein concentration assay over a wide range via surface-enhanced Raman scattering of Coomassie Brilliant Blue. Anal Chem 82(11):4325–4328. doi: 10.1021/ac100596u CrossRefGoogle Scholar
  26. 26.
    Bell SEJ, Sirimuthu NMS (2008) Quantitative surface-enhanced Raman spectroscopy. Chem Soc Rev 37(5):1012. doi: 10.1039/b705965p CrossRefGoogle Scholar
  27. 27.
    Kneipp K, Haka AS, Kneipp H, Badizadegan K, Yoshizawa N, Boone C, Shafer-Peltier KE, Motz JT, Dasari RR, Feld MS (2002) Surface-enhanced Raman spectroscopy in single living cells using gold nanoparticles. Appl Spectrosc 56(2):150–154CrossRefGoogle Scholar
  28. 28.
    Kneipp J, Kneipp H, McLaughlin M, Brown D, Kneipp K (2006) In vivo molecular probing of cellular compartments with gold nanoparticles and nanoaggregates. Nano Lett 6(10):2225–2231. doi: 10.1021/nl061517x CrossRefGoogle Scholar
  29. 29.
    Lu Y, Jiao R, Chen X, Zhong J, Ji J, Shen P (2008) Methylene blue-mediated photodynamic therapy induces mitochondria-dependent apoptosis in HeLa Cell. J Cell Biochem 105(6):1451–1460. doi: 10.1002/jcb.21965 CrossRefGoogle Scholar
  30. 30.
    Khdair A, Gerard B, Handa H, Mao G, Shekhar MPV, Panyam J (2008) Surfactant−polymer nanoparticles enhance the effectiveness of anticancer photodynamic therapy. Mol Pharm 5(5):795–807. doi: 10.1021/mp800026t CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Xi Guo
    • 1
  • Zhouyi Guo
    • 1
    Email author
  • Ying Jin
    • 1
  • Zhiming Liu
    • 1
  • Wen Zhang
    • 1
  • Deqiu Huang
    • 1
  1. 1.MOE Key Laboratory of Laser Life Science & Laboratory of Photonic Chinese Medicine, College of BiophotonicsSouth China Normal UniversityGuangzhouChina

Personalised recommendations