Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology , Tianjin University , Tianjin 300354 , China.
Langmuir. 2020 Feb 25;36(7):1804-1812. doi: 10.1021/acs.langmuir.9b03612. Epub 2020 Feb 11.
Deposition of amyloid-β (Aβ) aggregates in the brain is a main pathological hallmark of Alzheimer's disease (AD), so inhibition of Aβ aggregation has been considered as a promising strategy for AD prevention and treatment. Black phosphorus (BP) is a 2D nanomaterial with high biocompatibility and unique biodegradability, but its potential application in biomedicine suffers from the rapid degradability and unfunctionability. To overcome the drawbacks and broaden its application, we have herein designed an Aβ inhibitor (LK7)-coupled and polyethylene glycol (PEG)-stabilized BP-based nanosystem. The PEGylated-LK7-BP nanosheets (PEG-LK7@BP) not only exhibited a good stability but also demonstrated a significantly enhanced inhibitory potency on Aβ fibrillogenesis in comparison with its counterparts. This elaborately designed PEG-LK7@BP stopped the conformational transition and suppressed the fibrillization of Aβ, so it could completely rescue cultured cells from the toxicity of Aβ (by increasing the cell viability from 72 to 100%) at 100 μg/mL. It is considered that PEG-LK7@BP could bind Aβ species by enhanced electrostatic and hydrophobic interactions and thus efficiently alleviated Aβ-Aβ interactions. Meanwhile, the coupled LK7 on the BP surface formed a high local concentration that enhanced the affinity between the nanosystem and Aβ species. Finally, PEG could improve the stability and dispersibility of the nanoplatform to make it show an increased inhibitory effect on the amyloid formation. Hence, this work proved that PEG-LK7@BP is a promising nanosystem for the development of amyloid inhibitors fighting against AD.
淀粉样蛋白-β（Aβ）聚集体在大脑中的沉积是阿尔茨海默病（AD）的主要病理标志，因此抑制 Aβ 聚集已被认为是预防和治疗 AD 的一种有前途的策略。黑磷（BP）是一种具有高生物相容性和独特生物降解性的 2D 纳米材料，但由于其快速降解性和不可功能性，其在生物医学中的潜在应用受到限制。为了克服这些缺点并拓宽其应用范围，我们设计了一种 Aβ抑制剂（LK7）偶联和聚乙二醇（PEG）稳定的基于 BP 的纳米系统。PEG 化-LK7-BP 纳米片（PEG-LK7@BP）不仅表现出良好的稳定性，而且与对照相比，对 Aβ 纤维形成表现出显著增强的抑制作用。这种精心设计的 PEG-LK7@BP 阻止了构象转变并抑制了 Aβ 的纤维化，因此它可以在 100μg/mL 时完全使培养细胞免受 Aβ毒性的影响（使细胞活力从 72%增加到 100%）。据认为，PEG-LK7@BP 可以通过增强静电和疏水相互作用与 Aβ 结合，从而有效地减轻 Aβ-Aβ 相互作用。同时，BP 表面偶联的 LK7 形成了高局部浓度，增强了纳米系统与 Aβ 结合物之间的亲和力。最后，PEG 可以提高纳米平台的稳定性和分散性，使其对淀粉样形成表现出更高的抑制作用。因此，这项工作证明了 PEG-LK7@BP 是一种有前途的纳米系统，可用于开发针对 AD 的淀粉样蛋白抑制剂。
