Gold Nanoparticles with Adaptable Self-Assembled Monolayer Shells Allow Multivalent Inhibition and Sensing of...

Multivalent inhibitors that mimic the polysaccharide array on cells represent a new paradigm in the development of antiviral agents and antibiotics. Covalent ligand anchoring limits the affinity and, in turn, potency of these inhibitors with dissociation constants (K _d) commonly found in the micromolar or upper nanomolar range. Addressing this deficiency we here report on easily accessible gold core-shell nanoparticles (rSAM-NPs) featuring adaptable reversible self-assembled monolayer (rSAM)-based shells. The rSAMs are anchored by noncovalent amidinium-carboxylate interactions on gold nanoparticles at slightly alkaline pH resulting in laterally mobile pH-responsive assemblies that are functional at physiological pH. Introducing sialic acid ligands in the shell, we show that the rSAM-NPs strongly interact with the influenza virus surface protein hemagglutinin (limit of detection LoD < 2 nM) and deactivated bird flu virus H5N1 (LoD < 1 HAU) in allantoic liquid. Finally, we show that the rSAM-NPs effectively inhibit the interaction of the virus with red blood cells at concentrations in the low picomolar range. This represents a significant increase in potency with respect to multivalent inhibitors of similar size based on covalently anchored monosaccharides.