天然存在的糖胺聚糖（GAGs）是一类具有重要生物功能的细胞外成分。然而，它们的化学成分异质性以及纯化过程中的挑战成为了临床应用的主要缺点。因此，设计了各种合成糖聚合物来模拟天然GAGs的结构和功能。在本研究中，从结构简单的葡萄糖或N-乙酰葡萄糖胺单体合成了糖聚合物，进一步对其进行不同程度的硫酸化，并嫁接到二氧化硅纳米颗粒上，形成了直径均匀的球状纳米结构。由于多价效应的持续强化，所得糖聚合物纳米颗粒不仅通过稳定生长因子来促进细胞增殖，还通过削弱肿瘤细胞和活化血小板之间的黏附而显著抑制肿瘤转移。在制备的纳米颗粒中，具有N-乙酰葡萄糖胺片段和最高硫酸化程度的S3-PGNAc@Si表现出最强的生物活性，甚至接近肝素的活性。本研究提出了一种从简单且低成本的单糖中模拟天然GAGs的结构和功能的新方法，具有广泛的生物医学应用潜力。 版权所有 © 2023年。Elsevier B.V.出版。

Glycosaminoglycans (GAGs) are naturally existing extracellular components with a variety important biological functions. However, their heterogeneous chemical compositions and the challenges in purification have become the main disadvantages for clinical applications. Thus, various synthetic glycopolymers have been designed to mimic the structures and functions of natural GAGs. In the current study, glycopolymers from structurally simple glucose or N-acetylglucosamine monomers were synthesized, which were further subjected to sulfation of different degrees and grafting onto silica nanoparticles, leading to spherical-shaped nano-structures of uniform diameters. With the successively strengthened multivalent effect, the obtained glycopolymer nanoparticles not only showed excellent effects on promotion of cell proliferation by stabilizing growth factors, but also significantly inhibited tumor metastasis by weakening the adhesion between tumor cells and activated platelets. Among the prepared nanoparticles, S3-PGNAc@Si with N-acetylglucosamine segment and the highest sulfation degree exhibited the strongest bioactivities, which were even close to those of heparin. This work presents a novel approach for structural and functional mimicking of natural GAGs from simple and low-cost monosaccharides, holding great potential for a range of biomedical applications.Copyright © 2023. Published by Elsevier B.V.