Interestingly, the same trend was also observed for DC-SIGNR binding with Gx-DiMan. This result indicates that increasing GNP scaffold size is strongly beneficial for enhancing their MLGI affinities However, the trend of Dh -PGR relationship for DC-SIGN was found to be significantly different from that of DC-SIGNR; the latter consistently yielded larger Dhs than the former. The saturated Dhs for DC-SIGN binding with G13-DiMan and G27-DiMan were found to be ∼60 and ∼75 nm, respectively, which roughly match those expected for a single Gx-DiMan particle coated with a single layer of DC-SIGN molecules. In contrast, the Dhs of the Gx-DiMan-DC-SIGNR complexes (e.g., ∼200 and ∼500 nm for x = 13 and 27, respectively) were found to be too big to be isolated single particles, and thus indicating the formation of aggregation or cluster induced by DC-SIGNR and G13/G27-DiMan crosslinking. This result is comparable to that observed with G5-DiMan previously. Using a surface binding footprint of ~35 nm 2 per DC-SIGN molecule, and the glycan surface areas of Gx-DiMan calculated from their Dhs, a PGR of ~42 or ~92 with DC-SIGN was estimated to be able to fully saturate the surface of G13-DiMan or G27-DiMan, respectively.