Understanding the Adsorption of Peptides and Proteins onto PEGylated Gold Nanoparticles.

Yasiru Randika Perera,Alex C Hughes,Dhanush L Amarasekara,Nicholas C Fitzkee,Joanna Xiuzhu Xu,Ibraheem Abbood

doi:10.3390/molecules26195788

Yasiru Randika Perera, Alex C Hughes + Show 4 more

Open Access

https://doi.org/10.3390/molecules26195788

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Abstract

Polyethylene glycol (PEG) surface conjugations are widely employed to render passivating properties to nanoparticles in biological applications. The benefits of surface passivation by PEG are reduced protein adsorption, diminished non-specific interactions, and improvement in pharmacokinetics. However, the limitations of PEG passivation remain an active area of research, and recent examples from the literature demonstrate how PEG passivation can fail. Here, we study the adsorption amount of biomolecules to PEGylated gold nanoparticles (AuNPs), focusing on how different protein properties influence binding. The AuNPs are PEGylated with three different sizes of conjugated PEG chains, and we examine interactions with proteins of different sizes, charges, and surface cysteine content. The experiments are carried out in vitro at physiologically relevant timescales to obtain the adsorption amounts and rates of each biomolecule on AuNP-PEGs of varying compositions. Our findings are relevant in understanding how protein size and the surface cysteine content affect binding, and our work reveals that cysteine residues can dramatically increase adsorption rates on PEGylated AuNPs. Moreover, shorter chain PEG molecules passivate the AuNP surface more effectively against all protein types.

Highlights

amount of biomolecules to PEGylated gold nanoparticles (AuNPs) were incubated with an excess amount of different thiol Polyethylene glycol (PEG) compounds (PEG-SH) to fully passivate the surface
AuNP-PEG conjugates increase from −38 ± 3 mV to around −20 mV, indicating the negatively charged citrate-capped AuNP surfaces are all saturated with PEGs
Visualization of the PEG in Transmission electron microscopy (TEM) is difficult due to the formvar grids used in TEM experiments, and the PEG layer itself was not consistently observed (Figure S2, Supporting Information)

Summary

Introduction

When nanoparticles (NP) encounter a biological environment, biomolecules will spontaneously adsorb to the NP surface, forming a biomolecular corona. The NP surfaces are designed to elicit the adsorption of biomolecules for bioimaging and biosensing [1]. Some NP surfaces are fabricated to limit the adsorption of biomolecules, preventing recognition by the human body [2]. This is especially true for gold nanoparticles (AuNPs) that must pass through the blood–brain barrier or otherwise avoid clearance from the immune system [3,4]. When administered intravenously [5], AuNPs are rapidly removed from the circulation and accumulate mainly in the liver and the spleen due to the opsonization and recognition by phagocytes [3,6]

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