The integration of natural carbohydrates as ligands for the targeting of specific cell types into synthetic drug delivery systems such as polymer micelles has gained increasing attention, which is based on the expression of selective receptors or lectins in the cell membrane. While several structural aspects of this interaction are well-understood, only limited knowledge exists on the impact of the grafting density of sugar groups on this interaction. In the presented approach, we created core-shell-corona micelles with comparable size and shape, but a variable density of D-mannosylated chains sticking out from the surface, and investigated their interaction with the lectin concanavalin A (Con A). The polymers were synthesized using the reversible addition fragmentation chain transfer polymerization (RAFT) providing excellent control and narrow distributions for all materials. The blocks based on butyl acrylate and N-acryloyl morpholine form the core and shell of the micelles, respectively, while an additional D-mannosylated block, which forms the corona, is introduced applying a previously reported post-polymerisation functionalization of a reactive bromine precursor with a-D-thiomannose. Varying the ratios of the diblock and triblock polymers in the assembly process, the density of the D-mannosylated chains could easily be adjusted in this mixed micelles approach. All micelles revealed sizes of around 50 nm (estimated by light scattering and cryo-TEM) and similar morphologies, an aspect that is crucial for the direct evaluation of the influence of the grafting density on the binding affinity. The subsequent binding studies with the lectin Con A revealed a clear trend that binding affinity increases with increasing sugar content and a minimum of 10% of D-mannosylated chains is required for an effective and detectible aggregation. However, it is noteworthy that the full coverage of the micelles with sugar chains is detrimental for the binding to Con A and a significant reduction of the clustering rate was observed, while a ligand density of around 50e60% was favorable for the best interaction. These finding substantiate the importance of the ligand density for the design of targeting delivery systems. (C) 2017 Elsevier Ltd. All rights reserved.