Influence of Gold Glyconanoparticles on the Functioning of P-Glycoprotein In Vitro

Abstract

The aim of the work is to evaluate the effect of gold nanoparticles with a surface modified with fucose (Au-Fuc), lactose (Au-Lac), and galactose (Au-Gal) residues on the functional activity and expression of the transporter protein P-glycoprotein (Pgp). The work is performed using Caco-2 and HEK293 cells, which are incubated for 2 and 8 h with solutions of Au-Fuc, Au-Lac, and Au-Gal in a nutrient medium (450 and 300 µg/mL, 700 and 490 µg/mL, and 400 and 250 μg/mL, respectively). The amount of Pgp on the membranes of the Caco-2 cells is determined by the western blot method. The Pgp activity is assessed by the accumulation of fexofenadine Fex (150 µM) in cells by high-performance liquid chromatography (HPLC) with mass detection. Au-Fuc and Au-Gal do not change the amount of Pgp; Au-Lac increases the transporter level by 1.9 and 1.8 times upon 2 and 8 h of incubation respectively. Au-Fuc, Au-Lac, and Au-Gal increase the Pgp content in cells upon 8 h of incubation by 2.6, 3.5, and 5.3 times, which indicates a decrease in Pgp activity. When particles are incubated with HEK293 cells, no increase in the Fex levels are detected, which indicates the absence of a nonspecific increase in membrane permeability. Thus, the tested gold nanoparticles reduce the functional activity of Pgp in vitro.