Polymer Engineering and Colloid Science Laboratory, Department of Chemical Engineering, Indian Institute of Technology Madras , Chennai-600 036, India.
ACS Chem Neurosci. 2017 Oct 18;8(10):2325-2334. doi: 10.1021/acschemneuro.7b00238. Epub 2017 Aug 8.
Extracellular plaques of amyloid beta (Aβ) fibrils and neurofibrillary tangles are known to be associated with neurological diseases such as Alzheimer's disease. Studies have shown that spherical nanoparticles inhibit the formation of Aβ fibrils by intercepting the nucleation and growth pathways of fibrillation. In this report, gold nanorods (AuNRs) are used to inhibit the formation of Aβ fibrils and the shape-dependent plasmonic properties of AuNRs are exploited to faciliate faster dissolution of mature Aβ fibrils. Negatively charged, lipid (DMPC) stabilized AuNRs inhibit the formation of fibrils due to selective binding to the positevly charged amyloidogenic sequence of Aβ protein. The kinetics of inhibition is characterized by thioflavin T (ThT) fluorescence, transmission electronic microscopy (TEM), atomic force microscopy (AFM), and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). An increase in the aspect ratio of DMPC-AuNR in the range of 2.2-4.2 decreased the fibrils content proportionally. Further, the fibrils content is decreased by increasing the concentration of AuNR for all aspect ratios. As AuNR absorb near-infrared (NIR) light and creates a localized hotspot, NIR laser (800 nm) is applied for 2 min to facilitate the thermal dissolution of mature Aβ fibrils. Majority of Aβ fibrils are disintegrated into smaller fragments after exposure to NIR in the presence of AuNR. Thus, the DMPC-AuNRs exhibit a dual effect: inhibition of fibrillation and NIR laser facilitated dissolution of mature amyloid fibrils. This study essentially provides guidelines to design efficient nanoparticle-based therapeutics for neurodegenerative diseases.
细胞外淀粉样β（Aβ）纤维和神经原纤维缠结的斑块已知与阿尔茨海默病等神经退行性疾病有关。研究表明，球形纳米粒子通过阻断纤维形成的成核和生长途径来抑制 Aβ纤维的形成。在本报告中，使用金纳米棒（AuNRs）来抑制 Aβ纤维的形成，并利用 AuNR 的形状相关等离子体特性来促进成熟 Aβ纤维更快地溶解。带负电荷的脂质（DMPC）稳定的 AuNR 由于选择性结合 Aβ蛋白的阳性电荷淀粉样序列而抑制纤维的形成。通过噻唑蓝（ThT）荧光、透射电子显微镜（TEM）、原子力显微镜（AFM）和衰减全反射傅里叶变换红外光谱（ATR-FTIR）来表征抑制动力学。DMPC-AuNR 的纵横比在 2.2-4.2 范围内增加，纤维含量的比例相应降低。此外，对于所有纵横比，增加 AuNR 的浓度都会降低纤维含量。由于 AuNR 吸收近红外（NIR）光并产生局部热点，因此应用 NIR 激光（800nm）2 分钟以促进成熟 Aβ纤维的热溶解。在 AuNR 的存在下暴露于 NIR 后，大多数 Aβ纤维分解成较小的片段。因此，DMPC-AuNR 具有双重作用：抑制纤维形成和 NIR 激光促进成熟淀粉样纤维的溶解。这项研究为设计用于神经退行性疾病的高效基于纳米粒子的治疗方法提供了基本指导。
