Effect of Gold Nanoparticles and Coexisting Acetonitrile Solvent on the Structure of Bovine Serum Albumin

TL;DR

This study explores how gold nanoparticles and acetonitrile affect the structure of bovine serum albumin, which is important for designing drug delivery systems.

Contribution

The study reveals how coexisting organic solvents and nanoparticles influence protein structural stability in drug delivery systems.

Findings

AuNPs caused partial unfolding of BSA structure in the presence of acetonitrile.

MD simulations showed enhanced interactions between ACN and protein subdomains bound to AuNPs.

Water molecules interacted more with subdomains far from the nanoparticles.

Abstract

In the design of biocompatible protein-based drug delivery
systems
(DDS), the protein structural stability is important for its proper
function. While organic solvents widely used during the preparation
of protein-based DDS might induce structural changes in the proteins,
the presence of nanoparticles (NPs) might additionally alter the protein
structure. Although previous studies have reported various effects
of NPs on protein structure in various environments, there is a lack
of understanding of the effect of the coexisting organic solvent environment
on designing a biocompatible DDS. In this study, we investigated the
effect of 5 nm gold NPs (AuNPs) on albumin structural stability in
the presence of organic solvent, such as acetonitrile (ACN). Bovine
serum albumin (BSA) was chosen as an albumina transport protein
model with high abundance in the blood, high stability, and possible
applications in DDS. In addition, AuNPs were used in this study due
to their possible applications in DDS, therapeutics, sensing, imaging,
and biotechnology. ACN was chosen as an organic solvent with wide
applications in DDS and the pharmaceutical industry, and its concentration
was varied to investigate the effect of different solvent polarities.
Circular dichroism spectroscopy showed that the presence of AuNPs
caused partial unfolding of the BSA structure, with increased hydrodynamic
diameter distribution in the presence of 0%–15% vol. ACN. While
the most prominent effect was observed at 15% ACN, such results were
associated with enhanced protein-ACN interactions in the presence
of AuNPs, as revealed by MD simulations. Furthermore, while ACN molecules
strongly interacted with the protein subdomains bound to AuNPs, water
molecules had a higher propensity to interact with the subdomains
located far from the NP. Overall, such distinct interactions of protein
subdomains with water and coexisting organic solvents may enhance
the protein’s structural changes and unfolding in the presence
of NPs, leading to a better design of drug loading into proteins.

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