Surface modifications of nanoparticles can alter their physical and biological properties significantly. They effect particle aggregation, circulation times, and cellular uptake. This is particularly critical for the interaction with primary immune cells due to their important role in particle processing. We can show that the introduction of a hydrophilic PEG layer on the surface of the polysaccharide-based nanoparticles prevents unwanted aggregation under physiological conditions and decreases unspecific cell uptake in different primary immune cell types. The opposite effect can be observed with a parallel-performed introduction of a layer of low molecular weight dextran (3.5 and 5 kDa) on the particle surface (DEXylation) that encourages the nanoparticle uptake by antigen-presenting cells like macrophages and dendritic cells. Binding of DEXylated particles to these immune cells results in an upregulation of surface maturation markers and elevated production of proinflammatory cytokines, reflecting cell activation. Hence, DEXylated particles can potentially be used for passive targeting of antigen presenting cells with inherent adjuvant function for future immunotherapeutic applications.

中文翻译：

---

PEG和葡聚糖对多糖基纳米颗粒的表面修饰及其对免疫细胞结合和刺激特性的影响

纳米颗粒的表面改性可以显着改变其物理和生物学特性。它们影响颗粒聚集，循环时间和细胞摄取。由于其在颗粒加工中的重要作用，这对于与原代免疫细胞的相互作用特别重要。我们可以证明，在基于多糖的纳米颗粒的表面上引入亲水性PEG层可防止在生理条件下发生不必要的聚集，并减少不同初级免疫细胞类型中非特异性细胞的摄取。通过在颗粒表面平行引入一层低分子量右旋糖酐（3.5和5 kDa）可以观察到相反的效果（DEXylation），这可以促进抗原呈递细胞（如巨噬细胞和树突状细胞）吸收纳米颗粒。己糖基化的颗粒与这些免疫细胞的结合导致表面成熟标志物的上调和促炎细胞因子的产生增加，反映了细胞的活化。因此，DEX化颗粒可以潜在地用于具有固有佐剂功能的抗原呈递细胞的被动靶向，以用于将来的免疫治疗应用。