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Short-chained oligo(ethylene oxide)-functionalized gold nanoparticles: realization of significant protein resistance


Protein corona formed on nanomaterial surfaces play an important role in the bioavailability and cellular uptake of nanomaterials. Modification of surfaces with oligoethylene glycols (OEG) are a common way to improve the resistivity of nanomaterials to protein adsorption. Short-chain ethylene oxide (EO) oligomers have been shown to improve the protein resistance of planar Au surfaces. We describe the application of these EO oligomers for improved protein resistance of 30 nm spherical gold nanoparticles (AuNPs). Functionalized AuNPs were characterized using UV-Vis spectroscopy, dynamic light scattering (DLS), and zeta potential measurements. Capillary electrophoresis (CE) was used for separation and quantitation of AuNPs and AuNP-protein mixtures. Specifically, nonequilibrium capillary electrophoresis of equilibrium mixtures (NECEEM) was employed for the determination of equilibrium and rate constants for binding between citrate-stabilized AuNPs and two model proteins, lysozyme and fibrinogen. Semi-quantitative CE analysis was carried out for mixtures of EO-functionalized AuNPs and proteins, and results demonstrated a 2.5-fold to 10-fold increase in protein binding resistance to lysozyme depending on the AuNP surface functionalization and a 15-fold increase in protein binding resistance to fibrinogen for both EO oligomers examined in this study.

Using capillary electrophoresis, the addition of short-chained oligo(ethylene oxide) ligands to gold nanoparticles was shown to improve protein binding resistance up to 15-fold.

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KRR and CMS acknowledge funding and support from the National Academy of Sciences - National Research Council Postdoctoral Research Associateship Program. ITW recognizes the support of the NIST Summer Undergraduate Research Fellowship (SURF) Program.


This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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M. L. Walker and D. J. Vanderah conceived the initial project; I. T. Wood and M. L. Walker performed initial studies; K.R. Riley and C.M. Sims refined the project and contributed equally to essential experimentation and composition of the completed work.

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Correspondence to Kathryn R. Riley, Christopher M. Sims or Marlon L. Walker.

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Riley, K.R., Sims, C.M., Wood, I.T. et al. Short-chained oligo(ethylene oxide)-functionalized gold nanoparticles: realization of significant protein resistance. Anal Bioanal Chem 410, 145–154 (2018).

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  • Protein corona
  • Gold nanoparticles
  • Ethylene oxide
  • Binding constant
  • Capillary electrophoresis