Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Protocol
  • Published:

Polyethylene glycol-based bidentate ligands to enhance quantum dot and gold nanoparticle stability in biological media

Nature Protocols volume 4, pages 412–423 (2009)Cite this article

Abstract

We describe a simple and versatile scheme to prepare a series of poly(ethylene glycol)-based bidentate ligands that permit strong interactions with colloidal semiconductor nanocrystals (quantum dots, QDs) and gold nanoparticles (AuNPs) alike and promote their dispersion in aqueous solutions. These ligands are synthesized by coupling poly(ethylene glycol)s of various chain length to thioctic acid, followed by ring opening of the 1,2-dithiolane moiety to create a bidentate thiol anchoring group with enhanced affinity for CdSe-ZnS core-shell QDs. These ligands provide a straightforward means of preparing QDs and AuNPs that exhibit greater resistance to environmental changes, facilitating their effective use in bioassays and live cell imaging.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Synthetic scheme.
Figure 2: 1H-NMR spectra of some of the ligands.
Figure 3: FT-IR spectra of cap-exchanged QDs and AuNPs.
Figure 4: pH stability of cap-exchanged nanoparticles.
Figure 5: Cy3-peptide titration versus 530 nm emitting QDs.

Similar content being viewed by others

References

  1. Mattoussi, H., Kuno, M.K., Goldman, E.R., Anderson, G.P. & Mauro, J.M. Colloidal semiconductor quantum dot conjugates in biosensing. In Optical Biosensors: Present and Future (eds. Ligler, F.S. and Rowe Taitt, C.A.) 537–569 (Elsevier, Amsterdam, The Netherlands, 2002).

    Chapter  Google Scholar 

  2. Åkerman, M.E., Chan, W.C.W., Laakkonen, P., Bhatia, S.N. & Ruoslahti, E. Nanocrystal targeting in vivo . Proc. Natl. Acad. Sci. 99, 12617–12621 (2002).

    Article  PubMed  Google Scholar 

  3. Dubertret, B. et al. In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science 298, 1759–1762 (2002).

    Article  CAS  Google Scholar 

  4. Wu, X. et al. Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots. Nature Biotechnol. 21, 41–46 (2003).

    Article  CAS  Google Scholar 

  5. Jaiswal, J.K., Mattoussi, H., Mauro, J.M. & Simon, S.M. Long-term multiple color imaging of live cells using quantum dot bioconjugates. Nat. Biotechnol. 21, 47–51 (2003).

    Article  CAS  PubMed  Google Scholar 

  6. Goldman, E.R. et al. Conjugation of luminescent quantum dots with antibodies using an engineered adaptor protein to provide new reagents for fluoroimmunoassays. Anal. Chem. 74, 841–847 (2002).

    Article  CAS  PubMed  Google Scholar 

  7. Medintz, I.L. et al. Self-assembled biosensors based on quantum dot FRET donors. Nat. Mater. 2, 630–638 (2003).

    Article  CAS  PubMed  Google Scholar 

  8. Goldman, E.R. et al. Multiplexed toxin analysis using four colors of quantum dot fluororeagents. Anal. Chem. 76, 684–688 (2004).

    Article  CAS  PubMed  Google Scholar 

  9. Gao, X., Cui, Y., Levenson, R.M., Chung, L.W.K. & Nie, S. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat. Biotechnol. 22, 969–976 (2004).

    Article  CAS  PubMed  Google Scholar 

  10. Gerion, D. et al. Sorting fluorescent nanocrystals with DNA. J. Am. Chem. Soc. 124, 7070–7074 (2002).

    Article  CAS  PubMed  Google Scholar 

  11. Gerion, D. et al. Room-temperature single-nucleotide polymorphism and multiallele DNA detection using fluorescent nanocrystals and microarrays. Anal. Chem. 75, 4766–4772 (2003).

    Article  CAS  PubMed  Google Scholar 

  12. Kim, S. et al. Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nat. Biotechnol. 22, 93–97 (2004).

    Article  CAS  Google Scholar 

  13. Bruchez, M. Jr., Moronne, M., Gin, P., Weiss, S. & Alivisatos, A.P. Semiconductor nanocrystals as fluorescent biological labels. Science 281, 2013–2016 (1998).

    Article  CAS  Google Scholar 

  14. Chan, W.C.W. & Nie, S. Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281, 2016–2018 (1998).

    Article  CAS  PubMed  Google Scholar 

  15. Mattoussi, H. et al. Self-assembly of CdSe–ZnS quantum dot bioconjugates using an engineered recombinant protein. J. Am. Chem. Soc. 122, 12142–12150 (2000).

    Article  CAS  Google Scholar 

  16. Murray, C.B., Norris, D.J. & Bawendi, M.G. Synthesis and characterization of nearly monodisperse CdE (E=S, Se, Te) semiconductor nanocrystallites. J. Am. Chem. Soc. 115, 8706–8715 (1993).

    Article  CAS  Google Scholar 

  17. Hines, M.A. & Guyot-Sionnest, P. Synthesis and characterization of strongly luminescing ZnS-capped CdSe nanocrystals. J. Phys. Chem. 100, 468–471 (1996).

    Article  CAS  Google Scholar 

  18. Dabbousi, B.O. et al. (CdSe)ZnS core-shell quantum dots: synthesis and characterization of a size series of highly luminescent nanocrystallites. J. Phys. Chem. B 101, 9463–9475 (1997).

    Article  CAS  Google Scholar 

  19. Peng, Z.A. & Peng, X. Formation of high-quality CdTe, CdSe, and CdS nanocrystals using CdO as precursor. J. Am. Chem. Soc. 123, 183–184 (2001).

    Article  CAS  PubMed  Google Scholar 

  20. Peng, Z.A. & Peng, X. Nearly monodisperse and shape-controlled CdSe nanocrystals via alternative routes: nucleation and growth. J. Am. Chem. Soc. 124, 3343–3353 (2002).

    Article  CAS  PubMed  Google Scholar 

  21. Al-Jamal, W.T. et al. Lipid-quantum dot bilayer vesicles enhance tumor cell uptake and retention in vitro and in vivo . ACS Nano 2, 408–418 (2008).

    Article  CAS  PubMed  Google Scholar 

  22. Choi, H.S. et al. Renal clearance of quantum dots. Nature Biotechnol. 25, 1165–1170 (2007).

    Article  CAS  Google Scholar 

  23. Pinaud, F., King, D., Moore, H.-P. & Weiss, S. Bioactivation and cell targeting of semiconductor CdSe/ZnS nanocrystals with phytochelatin-related peptides. J. Am. Chem. Soc. 126, 6115–6123 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Pons, T., Uyeda, H.T., Medintz, I.L. & Mattoussi, H. Hydrodynamic dimensions, electrophoretic mobility, and stability of hydrophilic quantum dots. J. Phys. Chem. B 110, 20308–20316 (2006).

    Article  CAS  PubMed  Google Scholar 

  25. Medintz, I.L., Uyeda, H.T., Goldman, E.R. & Mattoussi, H. Quantum dot bioconjugates for imaging, labelling and sensing. Nat. Mater. 4, 435–446 (2005).

    Article  CAS  Google Scholar 

  26. Voura, E.B., Jaiswal, J.K., Mattoussi, H. & Simon, S.M. Tracking metastatic tumor cell extravasation with quantum dot nanocrystals and fluorescence emission-scanning microscopy. Nat. Med. 10, 993–998 (2004).

    Article  CAS  Google Scholar 

  27. Jaiswal, J.K., Goldman, E.R., Mattoussi, H. & Simon, S.M. Use of quantum dots for live cell imaging. Nat. Methods 1, 73–78 (2004).

    Article  PubMed  Google Scholar 

  28. Uyeda, H.T., Medintz, I.L., Jaiswal, J.K., Simon, S.M. & Mattoussi, H. Synthesis of compact mutidentate ligands to prepare stable hydrophilic quantum dot fluorophores. J. Am. Chem. Soc. 127, 3870–3878 (2005).

    Article  CAS  PubMed  Google Scholar 

  29. Mei, B.C. et al. Modular poly(ethylene glycol) ligands for biocompatible semiconductor and gold nanocrystals with extended pH and ionic stability. J. Mater. Chem. 18, 4949–4958 (2008).

    Article  CAS  Google Scholar 

  30. Medintz, I.L. et al. Proteolytic activity monitored by fluorescence resonance energy transfer through quantum-dot–peptide conjugates. Nat. Mater. 5, 581–589 (2006).

    Article  CAS  PubMed  Google Scholar 

  31. Qu, L., Peng, Z.A. & Peng, X. Alternative routes toward high quality CdSe nanocrystals. Nano Lett. 1, 333–337 (2001).

    Article  CAS  Google Scholar 

  32. Clapp, A.R., Goldman, E.R. & Mattoussi, H. Capping of CdSe-ZnS quantum dots with DHLA and subsequent conjugation with proteins. Nat. Protoc. 1, 1258–1267 (2006).

    Article  CAS  PubMed  Google Scholar 

  33. Turkevich, J., Stevenson, P.C. & Hillier, J. A study of the nucleation and growth processes in the synthesis of colloidal gold. Discuss. Faraday Soc. 11, 55–75 (1951).

    Article  Google Scholar 

  34. Grabar, K.C., Freeman, R.G., Hommer, M.B. & Natan, M.J. Preparation and characterization of Au colloid monolayers. Anal. Chem. 67, 735–743 (1995).

    Article  CAS  Google Scholar 

  35. Susumu, K. et al. Enhancing the stability and biological functionalities of quantum dots via compact multifunctional ligands. J. Am. Chem. Soc. 129, 13987–13996 (2007).

    Article  CAS  PubMed  Google Scholar 

  36. Sapsford, K.E. et al. Kinetics of metal-affinity driven self-assembly between proteins or peptides and CdSe-ZnS quantum dots. J. Phys. Chem. C 111, 11528–11538 (2007).

    Article  CAS  Google Scholar 

  37. Leatherdale, C.A., Woo, W.-K., Mikulec, F.V. & Bawendi, M.G. On the absorption cross section of CdSe nanocrystal quantum dots. J. Phys. Chem. B 106, 7619–7622 (2002).

    Article  CAS  Google Scholar 

  38. Clapp, A.R. et al. Fluorescence resonance energy transfer between quantum dot donors and dye-labeled protein acceptors. J. Am. Chem. Soc. 126, 301–310 (2004).

    Article  CAS  PubMed  Google Scholar 

  39. Clapp, A.R. et al. Quantum dot-based multiplexed fluorescence resonance energy transfer. J. Am. Chem. Soc. 127, 18212–18221 (2005).

    Article  CAS  PubMed  Google Scholar 

  40. Clapp, A.R., Medintz, I.L. & Mattoussi, H. Förster resonance energy transfer investigations using quantum-dot fluorophores. ChemPhysChem 7, 47–57 (2006).

    Article  CAS  PubMed  Google Scholar 

  41. Pons, T., Medintz, I.L., Wang, X., English, D.S. & Mattoussi, H. Solution-phase single quantum dot fluorescence resonance energy transfer. J. Am. Chem. Soc. 128, 15324–15331 (2006).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We acknowledge NRL, Office of Naval Research (ONR), the Army Research Office (ARO) and the CB Directorate/Physical S&T Division (DTRA) for financial support. We thank Dr Horn-Bond Lin for assistance with the FTIR spectra.

Author information

Authors and Affiliations

  1. Division of Optical Sciences, US Naval Research Laboratory, Washington, 20375, District of Columbia, USA

    Bing C Mei, Kimihiro Susumu & Hedi Mattoussi

  2. Department of Chemical Engineering, University of Massachusetts, Amherst, 01003, Massachusetts, USA

    Bing C Mei

  3. Center for Bio/Molecular Science and Engineering, US Naval Research Laboratory, Washington, 20375, District of Columbia, USA

    Igor L Medintz

Authors
  1. Bing C Mei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kimihiro Susumu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Igor L Medintz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hedi Mattoussi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hedi Mattoussi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mei, B., Susumu, K., Medintz, I. et al. Polyethylene glycol-based bidentate ligands to enhance quantum dot and gold nanoparticle stability in biological media. Nat Protoc 4, 412–423 (2009). https://doi.org/10.1038/nprot.2008.243

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nprot.2008.243

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing