"Sweet" Architecture-Dependent Uptake of Glycocalyx-Mimicking Nanoparticles Based on Biodegradable Aliphatic Polyesters by Macrophages
"Sweet" Architecture-Dependent Uptake of Glycocalyx-Mimicking Nanoparticles Based on Biodegradable Aliphatic Polyesters by Macrophages
复制标题
巨噬细胞对基于可生物降解脂肪族聚酯的糖萼模拟纳米颗粒的“甜蜜”结构依赖性摄取
DOI：
10.1021/jacs.7b07768
复制
发表时间：
2017-10-18
影响因子：
15
通讯作者：
Jiang, Ming
中科院分区：
文献类型：
--
作者：
Wu, Libin;Zhang, Yufei;Jiang, Ming
目前，由自组装糖聚合物制成的糖聚糖颗粒是细胞表面糖萼的实用且有效的模拟物。考虑到糖萼的复杂性，冠上具有不同糖的糖纳米粒子，即混合壳糖胶束，与同质壳胶束相比可能更有价值。在本文中，我们探讨了糖纳米粒子冠对糖聚糖粒子巨噬细胞、内吞作用和凝集素、结合能力的结构影响。设计并制备了一系列由半乳糖苷或甘露糖苷侧链功能化的可生物降解聚酯主链组成的糖纳米粒子。探索的不同结构是单组分（半乳糖苷或甘露糖苷）冠，由半乳糖苷甘露糖苷共聚物链制成的均匀混合冠（MG），以及由两种均糖聚合物构建的共混混合冠（M/G）。具有混合壳的纳米颗粒比具有单一糖成分的纳米颗粒在细胞摄取和凝集素结合方面表现出更高的效率。同时，出乎意料的是，尽管MG的粒径和甘露糖苷与半乳糖苷的比例相同，但它们的效率明显高于M/G。我们将这种明显的架构效应归因于 MG 和 M/G 之间的相位行为差异；即，前者具有均匀的冠，允许接触区域中更多的糖受体相互作用，而后者具有相分离，限制了两种糖单元与细胞受体的同时相互作用。
Glyconanopartides made by self-assembled glycopolymers currently are practical and efficient mimics of the glycocalyx on cell surfaces. Considering the complexity of the glycocalyx, glyconanoparticles with different sugars on their coronas, i.e., mixed-shell glycomicelles, could be more valuable compared to homoshell micelles. In this paper, we explore the architectural effect of the glycOnanoparticle corona on glycorianopartide Macrophage, endocytosis and lectin, binding ability. A series of glyconanoparticles composed of a biodegradable polyester backbone functionalized with galactoside or mannoside pendants were designed and prepared. The different architectures explored were single-component (galactoside or mannoside) coronas, homogeneously mixed coronas (MG) made by galactoside mannoside copolymer Chains, and blend-mixed coronas (M/G) constructed from two homoglycopolymers. Nanoparticles with a mixed shell showed a higher efficiency in cellular uptake and lectin-binding than those with a single sugar component. Meanwhile, unexpectedly, MG presented a significantly higher efficiency than M/G, although they had the same particle size and ratio of mannoside to galactoside. We attributed this apparent architectural effect to the difference in the phase behavior between MG and M/G; i.e., the former having a homogeneous corona allowed more sugar receptor interactions in the contact region, while the latter having phase separation limited the simultaneous interaction of the two kinds of sugar units with the cell receptors.