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自组装纳米伴侣抑制与2型糖尿病相关的人胰岛淀粉样多肽聚集。

Self-Assembled Nanochaperones Inhibit the Aggregation of Human Islet Amyloid Polypeptide Associated with Type 2 Diabetes.

作者信息

Niu Haihong, Hou Xiaoxue, Zhang Yanli, Wu Xiaohui, Deng Fei, Huang Fan, Shi Linqi, Ma Rujiang

机构信息

State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Functional Polymer Materials of Ministry of Education, College of Chemistry, Nankai University, Tianjin 300071, China.

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China.

出版信息

ACS Macro Lett. 2021 Jun 15;10(6):662-670. doi: 10.1021/acsmacrolett.1c00200. Epub 2021 May 11.

Abstract

Human islet amyloid polypeptide (hIAPP) aggregation is closely associated with dysfunction and apoptosis of pancreatic β-cells in type 2 diabetes (T2D). Accordingly, hIAPP amyloid inhibitors have shown promise against T2D. Here, by mimicking the function of natural molecular chaperones, nanochaperones (nChaps) based on self-assembled polymeric micelles with tunable surface microdomains for T2D treatment are reported. By capturing the aggregation-prone species of hIAPP onto the hydrophobic microdomains and segregating them by hydrophilic PEG chains, this kind of nChaps could effectively prevent hIAPP aggregation, block cell adhesion of hIAPP, facilitate hIAPP aggregates degradation and reduce hIAPP-related cytotoxicity. Therefore, our work will provide useful insights to develop a biomimetic strategy for the treatment of T2D.

摘要

人胰岛淀粉样多肽(hIAPP)聚集与2型糖尿病(T2D)中胰腺β细胞的功能障碍和凋亡密切相关。因此,hIAPP淀粉样蛋白抑制剂已显示出抗T2D的潜力。在此,通过模拟天然分子伴侣的功能,报道了基于具有可调节表面微区的自组装聚合物胶束用于T2D治疗的纳米伴侣(nChaps)。通过将易于聚集的hIAPP物种捕获到疏水微区上并用亲水性PEG链将它们隔离,这种nChaps可以有效防止hIAPP聚集,阻断hIAPP的细胞粘附,促进hIAPP聚集体降解并降低hIAPP相关的细胞毒性。因此,我们的工作将为开发治疗T2D的仿生策略提供有用的见解。

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