Abstract

Improving the design of nanoparticles for use as drug carriers or biosensors requires a better understanding of the protein–nanoparticle interaction. Here, we present a new tool to investigate this interaction in situ and without additional labeling of the proteins and/or nanoparticles. By combining nonresonant second-harmonic light scattering with a modified Langmuir model, we show that it is possible to gain insight into the adsorption behavior of blood proteins, namely fibrinogen, human serum albumin, and transferrin, onto negatively charged polystyrene nanoparticles. The modified Langmuir model gives us access to the maximum amount of adsorbed protein, the apparent binding constant, and Gibbs free energy. Furthermore, we employ the method to investigate the influence of the nanoparticle size on the adsorption of human serum albumin and find that the amount of adsorbed protein increases more than the surface area per nanoparticle for larger diameters.

Highlights

  • The interaction of nanoparticles with proteins has been of broad scientific interest, in the field of biomedical applications, where nanoparticles are commonly used as diagnostic agents and for drug delivery.[1−4] In the case of drug nanocarriers, the fate of the nanoparticles within the human body is determined by their interaction with blood proteins.[5]

  • Nonresonant second-harmonic generation (SHG) and such as second-harmonic (SHS) have been intensively used in the past to investigate charged planar and nanoparticle surfaces.[35−39,48−53] Commonly, second-order nonlinear optical processes are just considered to probe the interface

  • In the presence of charged moieties at the surface in contact with water, the electrostatic field generated at the surface leads to reorientation and polarization of water molecules

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Summary

Introduction

The interaction of nanoparticles with proteins has been of broad scientific interest, in the field of biomedical applications, where nanoparticles are commonly used as diagnostic agents and for drug delivery.[1−4] In the case of drug nanocarriers, the fate of the nanoparticles within the human body is determined by their interaction with blood proteins.[5]. Spectroscopic approaches have been extensively used to gain insight into the adsorption behavior, structure, and binding interactions of proteins on functionalized planar surfaces.[8−14] because of the comparable size between the object of interest and the used wavelength of these optical techniques, it is impossible to apply these methods to investigate nanoparticle surfaces in the same way they are applied to planar surfaces.[15] As in the case of their linear optical counterparts, this hurdle can be overcome by scattering methods, such as second-harmonic (SHS) or sumfrequency light scattering (SFS), which combine the surface specificity intrinsic to the nonlinear optical techniques with a scattering detection geometry and have been successfully employed to probe nanoparticle surfaces in situ.[15−19]

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