Glycoscience, despite its myriad of challenges, promises to unravel the causes of, potential new detection methods for, and novel therapeutic strategies against, many disease states. In the last two decades, glyco-gold nanoparticles have emerged as one of several potential new tools for glycoscientists. Glyco-gold nanoparticles consist of the unique structural combination of a gold nanoparticle core and an outer-shell comprising multivalent presentation of carbohydrates. The combination of the distinctive physicochemical properties of the gold core and the biological function/activity of the carbohydrates makes glyco-gold nanoparticles a valuable tool in glycoscience. In this review we present recent advances made in the use of one type of click chemistry, namely the azide–alkyne Huisgen cycloaddition, for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles.

The chemistry and interaction of thiones towards passivation, and self-assembly of metal nanoparticles is nascent and poorly understood. Here, we describe a sensitive (15 ppb) and rapid (<1 min) thiourea (TU) based self-assembly of citrate stabilized gold nanoparticles (AuNPs) into 1D arrays (or nanochains) through a non-crosslinking mechanism. The underlying principle for the nanochain formation is as follows: the displacement of negatively charged citrate with neutral TU in a Vromanlike effect introduces a surface polarity, which then drives the self-assembly of AuNPs into nanochains via the dipole-dipole interactions. Moreover, we find that the size of the nanochains can be controlled by regulating the strength of the resultant dipole, which depends on the physico-chemical parameters such as the zeta potential and hydrodynamic size. We further substantiate the dipole-based mechanistic pathway by demonstrating that addition of TU leads to a selective aggregation of electrostatically stabilized AuNP systems while sterically stabilized ones remain unaffected. The mechanism of ligand displacement (akin to Vroman effect) is supported by an increased sensitivity of the assembly process in the presence of NaHSO 4 . The soft-soft interactions of the gold-thione pair and the kinetics of ligand exchange were investigated and found to be influenced by the manner in which the substituents attached to the TU moiety modify the electron density around the thione sulphur. As demonstrated for TU detection (9.35 ppb) in sweet lime juice, the method serves as a simple, sensitive, selective, and rapid colorimetric assay for TU.

Gold nanoparticles decorated with full‐length sialic acid terminated complex bi‐antennary N‐glycans, synthesized with glycans isolated from egg yolk, were used as a sensor for the detection of both recombinant hemagglutinin (HA) and whole influenza A virus particles of the H1N1 subtype. Nanoparticle aggregation was induced by interaction between the sialic acid termini of the glycans attached to gold and the multivalent sialic acid binding sites of HA. Both dynamic light scattering (DLS) and UV/Vis spectroscopy demonstrated the efficiency of the sensor, which could detect viral HA at nanomolar concentrations and revealed a linear relationship between the extent of nanoparticle aggregation and the concentration of HA. UV/Vis studies also showed that these nanoparticles can selectively detect an influenza A virus strain that preferentially binds sialic acid terminated glycans with α(2→6) linkages over a strain that prefers glycans with terminal α(2→3)‐linked sialic acids.

The development of a galactose-capped gold nanoparticle-based colorimetric sensor for the detection of the lectin heat-labile enterotoxin is reported. Heat-labile enterotoxin is one of the pathogenic agents responsible for the intestinal disease called 'traveller's diarrhoea'. By means of specific interaction between galactose moieties attached to the surface of gold nanoparticles and receptors on the B-subunit of heat-labile enterotoxin (LTB), the gold nanoparticles reported here act as an efficient colorimetric sensor, which can detect the toxin at nanomolar concentrations. The effect of gold nanoparticle size on the detection sensitivity was investigated in detail. Amongst the various sizes of gold nanoparticles studied (2, 7, 12, and 20 nm), the 12 nm sized gold nanoparticles were found to be the most efficient, with a minimum heat-labile enterotoxin detection concentration of 100 nM. The red to purple colour change of the gold nanoparticle solution occurred within two minutes, indicating rapid toxin sensing.