Multifunctional peptide-assembled micelles for simultaneously reducing amyloid-β and reactive oxygen species,Chemical Science

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Multifunctional peptide-assembled micelles for simultaneously reducing amyloid-β and reactive oxygen species
Chemical Science ( IF 7.6 ) Pub Date : 2021-4-13 , DOI: 10.1039/d1sc00153a
Li Lei _{1,

2} , Zhifeng Zou ₁ , Jin Liu ₁ , Zhiai Xu ₁ , Ying Fu ₃ , Yang Tian ₁ , Wen Zhang ₄

Affiliation

The excessive production and deposition of amyloid-β (Aβ) is one of the most important etiologies of Alzheimer's disease (AD). The interaction between Aβ and metal ions produces aberrant reactive oxygen species (ROS), which induce oxidative stress and accelerate the progression of AD. To reduce Aβ plaques and ROS to maintain their homeostasis is an emerging and ingenious strategy for effective treatment of AD. Herein, we report the rational design of multifunctional micelles (MPGLT) based on a polymer-grafted peptide to simultaneously clear Aβ and ROS for AD therapy. The MPGLT integrating three functional peptides as a ROS scavenger (tk-GSH), β-sheet breaker (LP) and an autophagy activator (TK) respectively, could capture and degrade Aβ. Meanwhile, the tk-GSH on the surface of MPGLT effectively scavenges the intracellular ROS. Consequently, MPGLT reduced the cytotoxicity of Aβ and ROS. In vivo animal studies using an AD mouse model further showed that MPGLT could transport across the blood–brain barrier for decreasing the Aβ plaque and eliminating ROS in vivo. This peptide micelle-based synergistic strategy may provide novel insight for AD therapy.

中文翻译：

多功能肽组装胶束可同时减少淀粉样蛋白-β和活性氧

β淀粉样蛋白（Aβ）的过量产生和沉积是阿尔茨海默病（AD）最重要的病因之一。Aβ 与金属离子之间的相互作用产生异常的活性氧 (ROS)，从而诱发氧化应激并加速 AD 的进展。减少 Aβ 斑块和 ROS 以维持其稳态是有效治疗 AD 的新兴且巧妙的策略。在此，我们报告了基于聚合物接枝肽的多功能胶束（MPGLT）的合理设计，可同时清除 Aβ 和 ROS，用于 AD 治疗。MPGLT整合了三种功能肽，分别作为ROS清除剂（tk-GSH）、β-片层破坏剂（LP）和自噬激活剂（TK），可以捕获和降解Aβ。同时，MPGLT表面的tk-GSH有效清除细胞内的ROS。因此，MPGLT 降低了 Aβ 和 ROS 的细胞毒性。使用 AD 小鼠模型进行的体内动物研究进一步表明，MPGLT 可以穿过血脑屏障，从而减少体内Aβ 斑块并消除 ROS 。这种基于肽胶束的协同策略可能为 AD 治疗提供新的见解。

更新日期：2021-04-13

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