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

Niu, HH (Niu, Haihong) 1Hou, XX (Hou, Xiaoxue) 2, 3Zhang, YL (Zhang, Yanli) 1Wu, XH (Wu, Xiaohui) 1Deng, F (Deng, Fei) 1Huang, F (Huang, Fan) 2, 3Shi, LQ (Shi, Linqi) 1Ma, RJ (Ma, Rujiang) 1

ACS MACRO LETTERS, 2021, 10(6): 662-670

DOI 10.1021/acsmacrolett.1c00200

Abstract

Human islet amyloid polypeptide (hIAPP) aggregation is closely associated with dysfunction and apoptosis of pancreatic beta-cells in type 2 diabetes (T2D). Accordingly, hIAPP amyloid inhibitors have shown promise against T2D. Here, by mimicking the function of natural molecular chaperones, nano-chaperones (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.