Interaction of Human α-1-Acid Glycoprotein (AGP) with Citrate-Stabilized Gold Nanoparticles: Formation of Unexpectedly Strong Binding Events

Abstract

Numerous studies have investigated the interaction of high-abundance plasma proteins with different nanostructures. In this work, we focus on the interaction of citrate-stabilized spherical gold nanoparticles (Au-CIT) with human α-1-acid glycoprotein (AGP), one of the major acute phase proteins in humans with a normal plasma concentration between 0.6 and 1.2 mg mL–1, which can increase 4-fold in response to systemic tissue injury, inflammation, or infection. It is shown using different physicochemical approaches that AGP interaction not only takes place readily on Au-CIT nanoparticles, but the binding constant is as high as 1012 M–1, being several orders of magnitude larger than other highly abundant serum proteins. The adsorbed AGP preserved its biological identity and the formed Au-CIT/AGP particles were nontoxic to cells over a large concentration range. This is in contrast to positively charged gold nanostructures, which displayed lower binding affinity to AGP and higher cytotoxicity even at low particle concentrations. The in vivo investigations showed that the Au-CIT/AGP particles are mostly distributed in the liver and spleen and are absent in kidney and bladder as well as in peripheral organs like brain, confirming their confinement to the blood vessels.