Multivalent stimulation of β₁-, but not β₂-receptors by adrenaline functionalised gold nanoparticles

In this study, we present a strategy for the synthesis of catecholamine functionalised gold nanoparticles and investigated their multivalent interactions with adrenergic receptors in different biological systems. The catecholamines adrenaline and noradrenaline represent key examples of adrenergic agonists. We used gold nanoparticles as carriers and functionalised them on their surface with a variety of these neurotransmitter molecules. For this purpose, we synthesised each ligand separately using mercaptoundecanoic acid as a bifunctional linking unit and adrenaline (or noradrenaline) as a biogenic amine. This ligand was then immobilised onto the surface of presynthesised spherical monodispersive gold nanoparticles in a ligand exchange reaction. After detailed analytical characterisations, the functionalised gold nanoparticles were investigated for their interactions with adrenergic receptors in intestinal, cardiac and respiratory tissues. Whereas the contractility of respiratory smooth muscle cells (regulated by β₂-receptors) was not influenced, (nor)adrenaline functionalised nanoparticles administered in nanomolar concentrations induced epithelial K⁺ secretion (mediated via different β-receptors) and increased contractility of isolated rat cardiomyocytes (mediated by β₁-receptors). The present results suggest differences in the accessibility of adrenergic agonists bound to gold nanoparticles to the binding pockets of different β-receptor subtypes.