ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.
College of Environmental Science and Engineering, Shanghai Institute of Pollution Control and Ecological Security, Biomedical Multidisciplinary Innovation Research Institute, Shanghai East Hospital State Key Laboratory of Pollution Control and Resource Reuse, Tongji University, 1239 Siping Road, Shanghai, 200092, China.
Small. 2018 Nov;14(47):e1802825. doi: 10.1002/smll.201802825. Epub 2018 Oct 7.
Amyloid fibrils generally display chirality, a feature which has rarely been exploited in the development of therapeutics against amyloid diseases. This study reports, for the first time, the use of mesoscopic chiral silica nanoribbons against the in vivo amyloidogenesis of human islet amyloid polypeptide (IAPP), the peptide whose aggregation is implicated in type 2 diabetes. The thioflavin T assay and transmission electron microscopy show accelerated IAPP fibrillization through elimination of the nucleation phase and shortening of the elongation phase by the nanostructures. Coarse-grained simulations offer complementary molecular insights into the acceleration of amyloid aggregation through their nonspecific binding and directional seeding with the nanostructures. This accelerated IAPP fibrillization translates to reduced toxicity, especially for the right-handed silica nanoribbons, as revealed by cell viability, helium ion microscopy, as well as zebrafish embryo survival, developmental, and behavioral assays. This study has implicated the potential of employing chiral nanotechnologies against the mesoscopic enantioselectivity of amyloid proteins and their associated diseases.
淀粉样纤维通常表现出手性，这一特性在开发针对淀粉样疾病的治疗方法方面很少被利用。本研究首次报道了中观手性硅纳米带在体内人胰岛淀粉样多肽（IAPP）淀粉样形成中的应用，该肽的聚集与 2 型糖尿病有关。硫黄素 T 试验和透射电子显微镜显示，通过纳米结构消除成核阶段并缩短伸长阶段，加速了 IAPP 的纤维化。粗粒度模拟通过与纳米结构的非特异性结合和定向播种，提供了对加速淀粉样蛋白聚集的分子见解。这种加速的 IAPP 纤维化转化为毒性降低，特别是对于右手性硅纳米带，正如细胞活力、氦离子显微镜以及斑马鱼胚胎存活、发育和行为分析所揭示的那样。这项研究表明，在手性纳米技术的应用方面，有可能针对淀粉样蛋白及其相关疾病的中观对映选择性。
