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 α-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 50–60% was favorable for the best interaction. These finding substantiate the importance of the ligand density for the design of targeting delivery systems.

基于选择性受体或凝集素在细胞膜中的表达，将天然碳水化合物作为用于靶向特定细胞类型的配体整合到诸如聚合物胶束之类的合成药物传递系统中的问题日益引起人们的关注。尽管已经很好地理解了这种相互作用的几个结构方面，但是关于糖基的接枝密度对这种相互作用的影响只有有限的知识。在提出的方法中，我们创建了具有可比的尺寸和形状但密度可变的d的核-壳-电晕胶束。-甘露糖基化的链从表面伸出，并研究了它们与凝集素伴刀豆球蛋白A（Con A）的相互作用。使用可逆加成断裂链转移聚合（RAFT）合成聚合物，可为所有材料提供出色的控制效果和狭窄的分布。基于丙烯酸丁酯和N-丙烯酰基吗啉的嵌段分别形成胶束的核和壳，同时引入另一种形成电晕的d-甘露糖基化嵌段，采用先前报道的反应性溴前体的聚合后功能化与α- d-硫代甘露糖。在组装过程中改变二嵌段和三嵌段聚合物的比例，d的密度在这种混合胶束方法中，可以很容易地调节-甘露糖基化的链。所有胶束都显示出约50 nm的大小（通过光散射和冷冻-TEM估计）和相似的形态，这对直接评估接枝密度对结合亲和力的影响至关重要。随后用凝集素Con A进行的结合研究显示出明显的趋势，即结合亲和力随糖含量的增加而增加，且最小为d的10％。-甘露糖基化链是有效和可检测的聚集所必需的。但是，值得注意的是，胶束完全覆盖了胶束，不利于与Con A的结合，并且观察到聚集率显着降低，而约50-60％的配体密度有利于实现最佳相互作用。这些发现证实了配体密度对于靶向递送系统的设计的重要性。