Notwithstanding this slight underperformance of the new self-assembled dendrimers CholSG1, we decided to challenge them for heparin binding in 100% serum. Pleasingly, the MB assay returned for them a CE50 value of 0.69 ± 0.07 (corresponding to a dose of 0.63 mg/100 heparin IU), which is sensibly lower than that obtained for both C22G1 and protamine (0.96 and 0.79, respectively, Table 1). These good results led us back to the original hypothesis that the presence of a linear hydrocarbon chain in the C22G1 dendron may results in micelles more prone to degradation by the action of serum proteins (in particular HSA, the most abundant serum protein with high affinity for alkyl-bearing compounds), whilst the nanostructures arising from the self-assembling of CholSG1 might be less subjected to this disruptive protein action and, as such, can perform better in the more physiologically environment of 100% human serum.