Centre for Advanced Materials and School of Material Sciences, Indian Association for the Cultivation of Science, Kolkata 700032, India.
School of Bioscience, Indian Institute of Technology, Kharagpur 721302, India.
Biomacromolecules. 2020 Apr 13;21(4):1578-1586. doi: 10.1021/acs.biomac.0c00143. Epub 2020 Mar 11.
Intracellular/extracellular protein aggregation is linked to a variety of neurodegenerative diseases. Current research focuses on identifying antiamyloidogenic small molecules to inhibit such protein aggregation and associated cytotoxicity. We have recently demonstrated that transforming these antiamyloidogenic small molecules into nanoparticle forms can greatly improve their performance, and biocompatible/biodegradable formulation of such nanoparticles is critical for therapeutic applications. Here, we report polylactide (PL)-based biodegradable nanoparticles for improved neuroprotection against polyglutamine (polyQ) aggregation that is responsible for Huntington's disease. PL is terminated with an antiamyloidogenic trehalose molecule or the neurotransmitter dopamine, and the resultant nanoparticle is loaded with the antiamyloidogenic catechin molecule. The self-assembled nanoparticle is ∼200 nm in size and enters into the neuronal cell, inhibits polyQ aggregation, lowers oxidative stress, and enhances cell proliferation against polyQ aggregates. This biodegradable polymer can be used in nanoformulation of other reported antiamyloidogenic molecules for testing various animal models of neurodegenerative diseases.
细胞内外蛋白质聚集与多种神经退行性疾病有关。目前的研究重点是鉴定抗淀粉样蛋白的小分子，以抑制这种蛋白质聚集和相关的细胞毒性。我们最近证明，将这些抗淀粉样蛋白的小分子转化为纳米颗粒形式可以极大地提高它们的性能，并且此类纳米颗粒的生物相容性/可生物降解配方对于治疗应用至关重要。在这里，我们报告了基于聚乳酸（PL）的可生物降解纳米颗粒，以改善对多聚谷氨酰胺（polyQ）聚集的神经保护作用，polyQ 聚集是导致亨廷顿病的原因。PL 端接有抗淀粉样蛋白的海藻糖分子或神经递质多巴胺，所得纳米颗粒负载有抗淀粉样蛋白的儿茶素分子。自组装的纳米颗粒大小约为 200nm，并进入神经元细胞，抑制 polyQ 聚集，降低氧化应激，并增强对 polyQ 聚集物的细胞增殖。这种可生物降解的聚合物可用于其他报道的抗淀粉样蛋白分子的纳米制剂，以测试各种神经退行性疾病的动物模型。
