Terminal Structure of Triethylene Glycol-Tethered Chains on β-Cyclodextrin-Threaded Polyrotaxanes Dominates Temperature Responsivity and Biointeractions,Langmuir

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Terminal Structure of Triethylene Glycol-Tethered Chains on β-Cyclodextrin-Threaded Polyrotaxanes Dominates Temperature Responsivity and Biointeractions
Langmuir ( IF 3.7 ) Pub Date : 2021-09-03 , DOI: 10.1021/acs.langmuir.1c01894
Moe Ohashi ₁ , Atsushi Tamura ₁ , Nobuhiko Yui ₁

Affiliation

Pharmacological and biomedical applications of cyclodextrin (CD)-threaded polyrotaxanes (PRXs) have gained increasing attention. We had previously investigated the therapeutic effects of oligo(ethylene glycol) (OEG)-modified β-CD PRXs in congenital metabolic disorders. Although the chemical modification of PRXs is crucial for these applications, the influences of the chemical structure of OEG modified on PRXs were not completely understood. The current study focuses on the terminal group structures of triethylene glycol (TEG)-tethered chains, wherein three series of TEG-tethered PRXs (TEG–PRXs) with various TEG terminal group structures (hydroxy, methoxy, and ethoxy) were synthesized to investigate their physicochemical properties and biointeractions. The methoxy and ethoxy-terminated TEG–PRXs exhibited temperature-dependent phase transitions in phosphate buffer saline and formed coacervate droplets above their cloud points. A comprehensive analysis revealed that the hydrophobicity of the terminal group structures of the TEG-tethered chains played a dominant role in exhibiting temperature-dependent phase transition. Furthermore, the hydrophobicity of the terminal group structures of TEG-tethered chains on PRXs also affected the interactions with lipids and proteins, with the hydrophobic ethoxy-terminated TEG-tethered chains showing the highest interactions. However, in normal human skin fibroblasts, the moderately hydrophobic methoxy-terminated TEG-modified PRXs showed the highest intracellular uptake levels. As a result, we concluded that methoxy-terminated TEG is a suitable chemical modification for the biomedical applications of PRXs due to the negligible temperature responsivity around physiological temperature and significant intracellular uptake levels. The findings of this study shall contribute significantly to the rational design of PRXs and CD-based materials for future pharmacological and biomedical applications.

中文翻译：

β-环糊精螺纹聚轮烷上三甘醇系链的末端结构主导温度响应性和生物相互作用

环糊精 (CD) 螺纹聚轮烷 (PRX) 的药理学和生物医学应用越来越受到关注。我们之前曾研究过低聚（乙二醇）（OEG）修饰的 β-CD PRXs 在先天性代谢紊乱中的治疗效果。尽管 PRX 的化学修饰对于这些应用至关重要，但尚未完全了解修饰的 OEG 化学结构对 PRX 的影响。目前的研究侧重于三甘醇 (TEG) 系链的末端基团结构，其中合成了三个系列具有不同 TEG 端基结构（羟基、甲氧基和乙氧基）的 TEG 系链 PRX（TEG-PRX）以研究它们的理化性质和生物相互作用。甲氧基和乙氧基封端的 TEG-PRX 在磷酸盐缓冲盐水中表现出温度依赖性相变，并在其浊点上方形成凝聚层液滴。综合分析表明，TEG 系链的末端基团结构的疏水性在表现出温度依赖性相变中起主导作用。此外，PRX 上 TEG 连接链的末端基团结构的疏水性也影响了与脂质和蛋白质的相互作用，其中疏水性乙氧基终止的 TEG 连接链显示出最高的相互作用。然而，在正常人皮肤成纤维细胞中，适度疏水的甲氧基末端 TEG 修饰的 PRX 显示出最高的细胞内摄取水平。其结果，我们得出结论，甲氧基封端的 TEG 是一种适合 PRX 生物医学应用的化学修饰，因为它在生理温度附近的温度响应性可以忽略不计，并且细胞内摄取水平显着。这项研究的结果将为未来药理学和生物医学应用的 PRX 和基于 CD 的材料的合理设计做出重大贡献。

更新日期：2021-09-21

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