Nanocomposites Facilitate the Removal of AβFibrils for Neuroprotection  

作　　者：CHAI Jingshan LI Qiushi ZHAO Yu LIU Yang 

机构地区：[1]Key Laboratory of Functional Polymer Materials,Ministry of Education,State Key Laboratory of Medicinal Chemical Biology,College of Chemistry,Nankai University,Tianjin 300071,P.R.China

出　　处：《Chemical Research in Chinese Universities》2022年第2期522-528,共7页高等学校化学研究（英文版）

基　　金：supported by the National Key Research and Development Programs of China(No.2018YFA0209700);the Fund of the Frontiers Science Center for New Organic Matter,Nankai University,China(No.63181206);the National Natural Science Foundation of China(Nos.22077073,22007051);the Fundamental Research Funds for the Central Universities,Nankai University,China(No.63206015);the China Postdoctoral Science Foundation (No.2019M660975).

摘　　要：Accumulation of β-amyloid(Aβ) fibrils in the brain is one of the main culprits in Alzheimer’s disease(AD) progression, which initiates the neuronal damage and subsequent neurodegeneration. Various anti-Aβ agents have shown the potentials to dissociate Aβ fibrils. However, these approaches can’t facilitate the removal of Aβ fibrils, resulting in a disappointing therapeutic effect. Herein, we demonstrate an integrated polymer nanocomposite(NP-GLVFF-IgG) that can dissociate Aβ fibrils into fragments and activate microglia to remove the fragments via Fc receptors-mediated phagocytosis. NP-GLVFF-IgG is constructed by an albumin/polymer hybrid nanoparticle with Gly-Leu-Val-Phe-Phe (GLVFF) peptides and Immunoglobulin G(IgG) molecules on the surface. In this design, NP-GLVFF-IgG achieves to dissociate the Aβ fibrils by the strong hydrogen-bonding interactions between Aβ fibrils and GLVFF peptides. Then, NP-GLVFF-IgG activates the microglial phagocytosis, thereby achieving an enhanced phagocytic removal of Aβ fibrils for neuroprotection. Moreover, NP-GLVFF-IgG achieves to trigger the effective removal of Aβ fibrils even under inflammatory condition that usually suppressed phagocytosis. Therefore, NP-GLVFF-IgG has great potential as a novel therapeutic platform for effective AD therapy.

关 键 词：Alzheimer’s disease Aβfibril Nanocomposite Hydrogen-bonding interaction MICROGLIA 

分 类 号：TB33[一般工业技术—材料科学与工程]