Composite of gold nanoclusters and basified human serum albumin significantly boosts the inhibition of Alzheimer's β-amyloid by photo-oxygenation

Wei Liu; Hui Zhang; Xiaoyan Dong; Yan Sun

doi:10.1016/j.actbio.2022.03.019

Composite of gold nanoclusters and basified human serum albumin significantly boosts the inhibition of Alzheimer's β-amyloid by photo-oxygenation

Acta Biomater. 2022 May:144:157-167. doi: 10.1016/j.actbio.2022.03.019. Epub 2022 Mar 14.

Authors

Wei Liu¹, Hui Zhang¹, Xiaoyan Dong¹, Yan Sun²

Affiliations

¹ Department of Biochemical Engineering, School of Chemical Engineering and Technology and Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China.
² Department of Biochemical Engineering, School of Chemical Engineering and Technology and Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China. Electronic address: ysun@tju.edu.cn.

PMID: 35301147
DOI: 10.1016/j.actbio.2022.03.019

Abstract

Photo-oxygenation has become an effective way to inhibit Alzheimer's β-amyloid protein (Aβ) fibrillogenesis, which involves oxidative modification of Aβ by photo-oxidants. However, limitations of the current photo-oxidants, such as low biocompatibility and low affinity for Aβ, hinder the progression of the photo-oxygenation strategy. Herein, using human serum albumins (HSA) with binding affinity for Aβ as a platform, we have fabricated HSA-stabilized gold nanoclusters (AuNCs@HSA) and further modified the AuNCs@HSA with ethylenediamine to create basified HSA (HSA-B)-stabilized AuNCs. The basified composite, AuNCs@HSA-B, showed significantly higher potency on the inhibition of β-amyloid formation and capability of reactive oxidative species generation than AuNCs@HSA. In addition to the inhibition effect, under near-infrared (NIR) laser irradiation, AuNCs@HSA-B generated singlet oxygen to oxygenate Aβ monomers, distinctly alleviating Aβ-mediated neurotoxicity at a low concentration. In vivo studies demonstrated that NIR-activated AuNCs@HSA-B promoted the lifespan extension of transgenic C. elegans strain CL2006 by decreasing the Aβ burden. This well-designed AuNCs@HSA-B integrates inhibition, Aβ targeting, and photo-oxygenation, providing new insights into the development of protein-based photo-oxidant against Alzheimer's β-amyloid. STATEMENT OF SIGNIFICANCE: Alzheimer's disease (AD) has been threatening human health for more than 100 years. Recently, researchers have focused on inhibiting β-amyloid protein (Aβ) aggregation by exploring photo-excited biomaterials, which enable modulation of Aβ fibrillization with high spatiotemporal controllability. The present work demonstrates the fabrication of basified human serum albumins (HSA-B)-stabilized gold nanoclusters (AuNCs@HSA-B), and shows the potential of this near-infrared (NIR) laser-activated AuNCs@HSA-B as a photo-oxidant against Aβ aggregation by photo-oxygenation. Our work should open a new horizon in the design of protein-based photo-oxidant for treating AD in the future.

Keywords: Alzheimer's disease; Nanoclusters, inhibition; Photo-oxygenation; β-amyloid protein.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / drug therapy
Amyloid beta-Peptides* / metabolism
Animals
Caenorhabditis elegans / metabolism
Gold / pharmacology
Humans
Oxidants
Serum Albumin, Human

Substances

Amyloid beta-Peptides
Oxidants
Gold
Serum Albumin, Human