Ligand Design and Synthesis. A lipoic acid-tetra(ethylene glycol)-α-manno-α-1,2-biose (LA-EG4-DiMan) based multifunctional ligand was synthesised via our established procedures (see Fig. for its chemical structure). Each ligand was designed to contain three unique functional domains: a LA anchoring domain to chelate strongly on the GNP surface by forming two strong Au-S bonds; a hydrophilic flexible EG4 linker domain to offer high water solubility, excellent biocompatibility and resistance against non-specific interactions; and a terminal DiMan domain to promote strong and specific binding with DC-SIGN/R. A hydroxyl group (OH) terminating ligand having the same anchoring and EG4 linker domains, LA-EG4-OH, (see Fig. for its chemical structure) was also synthesized and employed as a spacer ligand to tune the GNP surface glycan density. It also served as a negative control to correct the fluorescence quenching background (in the absence of specific MLGIs) caused by GNP's inner filter effect. We showed previously that displaying LA-EGn-DiMan based glycan ligands polyvalently onto QDs (n = 3, 11) or G5 (n = 2) 11 yielded strong MLGI affinities with DC-SIGN, while those coated with the equivalent OH terminating ligands (with no terminal DiMan group) gave no measurable binding, suggesting that LA-EG4-OH is a suitable negative control ligand here.