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Multifunctional ligands based on dihydrolipoic acid and polyethylene glycol to promote biocompatibility of quantum dots

Nature Protocols volume 4, pages 424–436 (2009)Cite this article

Abstract

One of the common strategies to promote the transfer of quantum dots (QDs) to buffer media and to couple them to biological molecules has relied on cap exchange. We have shown previously that dihydrolipoic acid (DHLA) and polyethylene glycol (PEG)-appended DHLA can effectively replace the native ligands on CdSe-ZnS QDs. Here we explain in detail the synthesis of a series of modular ligands made of the DHLA-PEG motif appended with terminal functional groups. This design allows easy coupling of biomolecules and dyes to the QDs. The ligands are modular and each is comprised of three units: a potential biological functional group (biotin, carboxylic acid and amine) and a DHLA appended at the ends of a short PEG chain, where PEG promotes water solubility and DHLA provides anchoring onto the QD. The resulting QDs are stable over a broad pH range and accessible to simple bioconjugation techniques, such as avidin–biotin binding.

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Figure 1: Modular design of hydrophilic ligands with terminal functional groups used in this study.
Figure 2: Chemical structures and synthetic routes of the surface ligands used in this study.
Figure 3: FT-IR spectra for ligands produced in this study.
Figure 4: Surface-binding assays of biotin-modified QDs to NeutrAvidin-functionalized surfaces.
Figure 5: Absorption and emission spectra of EDC-coupled QD-dye conjugates.

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Acknowledgements

We acknowledge NRL, Office of Naval Research (ONR) and the Army Research Office for financial support. We thank Drs Horn-Bond Lin and Igor Medintz for assistance.

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Authors and Affiliations

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

    Kimihiro Susumu, Bing C Mei & Hedi Mattoussi

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

    Bing C Mei

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  1. Kimihiro Susumu
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Correspondence to Hedi Mattoussi.

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Susumu, K., Mei, B. & Mattoussi, H. Multifunctional ligands based on dihydrolipoic acid and polyethylene glycol to promote biocompatibility of quantum dots. Nat Protoc 4, 424–436 (2009). https://doi.org/10.1038/nprot.2008.247

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