Nanocomposites Facilitate the Removal of Aβ Fibrils for Neuroprotection

doi:10.1007/s40242-021-1372-3

高等学校化学研究 ›› 2022, Vol. 38 ›› Issue (2): 522-528.doi: 10.1007/s40242-021-1372-3

Nanocomposites Facilitate the Removal of Aβ Fibrils for Neuroprotection

CHAI Jingshan, LI Qiushi, ZHAO Yu, LIU Yang

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

收稿日期:2021-09-16 修回日期:2021-11-09 出版日期:2022-04-01 发布日期:2021-11-12
通讯作者: ZHAO Yu, LIU Yang E-mail:chemyzhao@nankai.edu.cn;yliu@nankai.edu.cn
基金资助:
This work was 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) and the China Postdoctoral Science Foundation (No.2019M660975).

Nanocomposites Facilitate the Removal of Aβ Fibrils for Neuroprotection

CHAI Jingshan, LI Qiushi, ZHAO Yu, LIU Yang

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

Received:2021-09-16 Revised:2021-11-09 Online:2022-04-01 Published:2021-11-12
Contact: ZHAO Yu, LIU Yang E-mail:chemyzhao@nankai.edu.cn;yliu@nankai.edu.cn
Supported by:
This work was 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) and the China Postdoctoral Science Foundation (No.2019M660975).

摘要/Abstract

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, Aβ fibril, Nanocomposite, Hydrogen-bonding interaction, Microglia

Abstract: 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.

Key words: Alzheimer’s disease, Aβ fibril, Nanocomposite, Hydrogen-bonding interaction, Microglia

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CHAI Jingshan, LI Qiushi, ZHAO Yu, LIU Yang. Nanocomposites Facilitate the Removal of Aβ Fibrils for Neuroprotection[J]. 高等学校化学研究, 2022, 38(2): 522-528.

CHAI Jingshan, LI Qiushi, ZHAO Yu, LIU Yang. Nanocomposites Facilitate the Removal of Aβ Fibrils for Neuroprotection[J]. Chemical Research in Chinese Universities, 2022, 38(2): 522-528.

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[1]	GAO Huimin, SHI Rui, ZHU Youliang, QIAN Hujun and LU Zhongyuan. Coarse-grained Dynamics Simulation in Polymer Systems: from Structures to Material Properties[J]. 高等学校化学研究, 2022, 38(3): 653-670.
[2]	Hakan, AHAL, Gülben TORĞUT, Erdal CANPOLAT. Optimization of Electrical Conductivity of SA-graphene Nanocomposites Using Response Surface Methodology[J]. 高等学校化学研究, 2022, 38(2): 596-602.
[3]	LAN Weifei, HU Ruifeng, HUANG Danrong, DONG Xu, SHEN Gangyi, CHANG Shan, DAI Dongsheng. Palladium Nanoparticles/Graphdiyne Oxide Nanocomposite with Excellent Peroxidase-like Activity and Its Application for Glutathione Detection[J]. 高等学校化学研究, 2022, 38(2): 529-534.
[4]	PAN Chuanqi, LIU Xiaoxuan, ZHANG Xiang, MAO Feihong, XU Peiyan, ZHU Yuhua, DENG Hongtao, LUO Zhu, SUN Hongwei, ZHANG Lizhi, GUO Yanbing. Fabrication and Excellent Antibacterial Activity of Well-defined CuO/Graphdiyne Nanostructure[J]. 高等学校化学研究, 2021, 37(6): 1341-1347.
[5]	XIANG Siyuan, MENG Qingnan, ZHANG Kai, GU Yue, LIU Wendong, YANG Bai. Facile Synthesis of ZnO-Au Nanopetals and Their Application for Biomolecule Determinations[J]. 高等学校化学研究, 2019, 35(5): 924-928.
[6]	WU Shuo, YANG Xinlan, ZHAO Yanqiu. Ru(II) Bipyridyl Complex and TiO₂ Nanocomposite Based Biomolecule-free Photoelectrochemical Sensor for Highly Selective Determination of Ultra-trace Hg²⁺ in Aqueous Systems[J]. 高等学校化学研究, 2019, 35(3): 370-376.
[7]	GUAN Renquan, ZHAI Hongju, SUN Dewu, ZHANG Junkai, WANG Yan, LI Jiaxin. Effects of Ag Doping Content and Dispersion on the Photocatalytic and Antibacterial Properties in ZnO Nanoparticles[J]. 高等学校化学研究, 2019, 35(2): 271-276.
[8]	HAN Donglai, LI Boxun, XING Guoliang, ZHANG Yuanyuan, CHEN Yue, SUN Yantao, ZHANG Yongjun, LIU Yang, YANG Jinghai. Facile Synthesis of Fe₃Pt-Ag Nanocomposites for Catalytic Reduction of Methyl Orange[J]. 高等学校化学研究, 2018, 34(6): 871-876.
[9]	ZHANG Jindi, WANG Jun, ZHAO Lina, YANG Wenlong, BI Meng, WANG Yuchang, NIU Hongyan, LI Yuxin, WANG Binsong, GAO Yachen, LI Chensha, HUANG Xuezhen. Photo Responsive Silver Nanoparticles Incorporated Liquid Crystalline Elastomer Nanocomposites Based on Surface Plasmon Resonance[J]. 高等学校化学研究, 2017, 33(5): 839-846.
[10]	LI Xiaoshuang, LIU Yuan, GUO Chaofeng, LIU Haiyang, WANG Gang, CAI Qiang, YAO Youwei. Influence of Layered Aluminoborophosphate on Flame Retardance, Crystallization Behaviors and Mechanical Properties of Polyamide 66 Systems[J]. 高等学校化学研究, 2016, 32(1): 127-133.
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Nanocomposites Facilitate the Removal of Aβ Fibrils for Neuroprotection

Nanocomposites Facilitate the Removal of Aβ Fibrils for Neuroprotection

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