Abstract：
Glucose has been extensively studied as a targeting ligand on nanoparticles for biomedical nanoparticles. A promising nanocarrier platform are single-chain polymer nanoparticles (SCNPs). SCNPs are well-defined 5-20 nm semi-flexible nano-objects, formed by intramolecularly crosslinked linear polymers. Functionality can be incorporated by introducing labile pentafluorophenyl (PFP) esters in the polymer backbone, which can be readily substituted by functional amine-ligands. However, not all ligands are compatible with PFP-chemistry, requiring different ligation strategies for increasing versatility of surface functionalization. Here, we combine active PFP-ester chemistry with copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) click chemistry to yield dual-reactive SCNPs. First, the SCNPs are functionalized with increasing amounts of 1-amino-3-butyne groups through PFP-chemistry, leading to a range of butyne-SCNPs with increasing terminal alkyne-density. Subsequently, 3-azido-propylglucose is conjugated through the glucose C1- or C6-position by CuAAC click chemistry, yielding two sets of glyco-SCNPs. Cellular uptake is evaluated in HeLa cancer cells, revealing increased uptake upon higher glucose-surface density, with no apparent positional dependance. The general conjugation strategy proposed here can be readily extended to incorporate a wide variety of functional molecules to create vast libraries of multifunctional SCNPs.
摘要：
已经广泛研究了葡萄糖作为生物医学纳米颗粒的纳米颗粒上的靶向配体。一个有前途的纳米载体平台是单链聚合物纳米颗粒（SCNP）。SCNP是定义明确的5-20nm半柔性纳米物体，由分子内交联的线性聚合物形成。官能团可以通过在聚合物主链中引入不稳定的五氟苯基(PFP)酯来引入,其可以容易地被官能胺配体取代。然而,并非所有配体都与PFP化学相容，需要不同的连接策略来增加表面功能化的多功能性。这里,我们将活性PFP-酯化学与铜(I)-催化的叠氮化物炔环加成(CuAAC)点击化学结合以产生双反应性SCNP。首先,通过PFP化学，SCNP被增加量的1-氨基-3-丁炔基团官能化，随着末端炔烃密度的增加，产生一系列丁炔烃-SCNP。随后，3-叠氮基丙基葡萄糖通过CuAAC点击化学通过葡萄糖C1-或C6-位置缀合，产生两组糖-SCNP。在HeLa癌细胞中评估细胞摄取，揭示了更高的葡萄糖表面密度的摄取增加，没有明显的位置依赖性。本文提出的一般缀合策略可以容易地扩展到并入各种各样的功能分子以产生大量的多功能SCNP文库。
