As shown in Table , the binding ΔH 0 values obtained from the GNP fluorescent quenching assay agreed very well with those obtained by ITC, thereby confirming that our GNP based fluorescence quenching can be used as a reliable method to probe MLGI thermodynamic parameters. Specifically, both G5-and G13-psDiMan100% binding with DC-SIGN were found to be enthalpy driven, with comparable negative ΔH 0 s of ~-95 KJ.mol -1 (Table , Fig. ). Interestingly, their multivalent binding ΔH 0 s are about 4 time of that of psDiMan-DC-SIGN monovalent binding obtained from ITC (e.g., -23.4 kJ.mol -1 , see SI, Fig. ), indicating that all 4 CRDs in DC-SIGN are engaged in Gx-psDiMan binding. This is also fully consistent with the DLS results described in the earlier section, where the saturated Dhs of Gx-psDiMan-DC- ITC studies on DC-SIGN binding to Gx-psDiMan50% gave similar binding H 0 values (e.g., -99.4 ± 2.7 and -93.6± 1.5 kJ/mol for x = 5 and 13, respectively, see SI, Fig. ) to those of Gx-psDiMan100%, indicating the same tetravalent binding mode. These results are fully consistent with the glycan content dependent DC-SIGN binding affinity studies described in the earlier section (Fig. , Table ). Since the psDiMan contents in both Gx-psDiMan-50% and 100% are higher than the minimal glycan density threshold, all 4 binding sites in each DC-SIGN molecule should be able to engage in binding with psDiMan groups from the same Gx-psDiMan particle to yield the maximal binding valency.