Design of Multifunctional Agent Based on Basified Serum Albumin for Efficient In Vivo β-Amyloid Inhibition and Imaging,ACS Applied Bio Materials

当前位置： X-MOL 学术 › ACS Appl. Bio Mater. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Design of Multifunctional Agent Based on Basified Serum Albumin for Efficient In Vivo β-Amyloid Inhibition and Imaging
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2020-04-22 , DOI: 10.1021/acsabm.0c00295
Wenjuan Wang ₁ , Wei Liu ₁ , Shaoying Xu ₁ , Xiaoyan Dong ₁ , Yan Sun ₁

Affiliation

Theranostics, the combination of therapeutics and diagnostics, has emerged as a sophisticated, integrated, and advanced tool in the prevention and treatment of serious diseases, such as Alzheimer’s disease (AD). However, the preclinical research of an AD theranostic molecule is in its infancy and needs to be explored in depth. Herein, a multifunctional theranostic agent is designed and fabricated by conjugating an Aβ-specific near-infrared (NIR) fluorescence probe (F) and by coupling a BBB penetrable peptide (Penetratin, Pen) onto the basified human serum albumin (HSA-B) that has been recently proven as an effective amyloid-β (Aβ) inhibitor. Such an elaborately constructed HSA-B-based molecule (HSA-BFP) possesses high potency on inhibiting Aβ fibrillogenesis, for example, increasing SH-SY5Y cell viability from 66.5 to 93%. In addition, HSA-BFP exhibits favorable stability in the “off–on” NIR imaging of Aβ plaques and achieves a 2-fold increase of BBB permeability after the Pen modification. More importantly, in vivo assays with the AD model C. elegans CL2006 indicate that HSA-BFP can specifically image Aβ deposits, decrease amyloid accumulation, and attenuate Aβ-triggered paralysis. Thus, HSA-B has been proven as a potent and versatile platform for the development of AD theranostic agents.

中文翻译：

基于碱化血清白蛋白的高效体内β-淀粉样蛋白抑制和成像多功能药剂的设计

治疗诊断学是治疗学和诊断学的结合，已成为预防和治疗阿尔茨海默病 (AD) 等严重疾病的复杂、综合和先进的工具。然而，AD治疗分子的临床前研究尚处于起步阶段，需要深入探索。在此，通过结合 Aβ 特异性近红外 (NIR) 荧光探针 ( F) 并通过将 BBB 可穿透肽 (Penetratin, Pen) 偶联到最近被证明是有效的淀粉样蛋白-β (Aβ) 抑制剂的碱化人血清白蛋白 (HSA-B) 上。这种精心构建的基于 HSA-B 的分子 (HSA-BFP) 具有抑制 Aβ 原纤维生成的高效力，例如，将 SH-SY5Y 细胞活力从 66.5% 提高到 93%。此外，HSA-BFP 在 Aβ 斑块的“关-开”近红外成像中表现出良好的稳定性，并且在 Pen 修饰后 BBB 通透性增加了 2 倍。更重要的是，使用 AD 模型进行体内测定C. elegansCL2006 表明 HSA-BFP 可以特异性地成像 Aβ 沉积物，减少淀粉样蛋白的积累，并减轻 Aβ 引发的麻痹。因此，HSA-B 已被证明是用于开发 AD 治疗诊断剂的有效且多功能的平台。

更新日期：2020-04-22

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南