Few-layer bismuth selenides exfoliated by hemin inhibit amyloid-β1–42 fibril formation

Jian Peng,Yunjing Xiong,Liping Sun,Zhiqin Lin,Jian Weng

doi:10.1038/srep10171

Abstract

Inhibiting amyloid-β (Aβ) fibril formation is the primary therapeutic strategy for Alzheimer’s disease. Several small molecules and nanomaterials have been used to inhibit Aβ fibril formation. However, insufficient inhibition efficiency or poor metabolization limits their further applications. Here, we used hemin to exfoliate few-layer Bi2Se3 in aqueous solution. Then we separated few-layer Bi2Se3 with different sizes and thicknesses by fractional centrifugation, and used them to attempt to inhibit Aβ1-42 aggregation. The results show that smaller and thinner few-layer Bi2Se3 had the highest inhibition efficiency. We further investigated the interaction between few-layer Bi2Se3 and Aβ1-42 monomers. The results indicate that the inhibition effect may be due to the high adsorption capacity of few-layer Bi2Se3 for Aβ1−42 monomers. Few-layer Bi2Se3 also decreased Aβ-mediated peroxidase-like activity and cytotoxicity according to in vitro neurotoxicity studies under physiological conditions. Therefore, our work shows the potential for applications of few-layer Bi2Se3 in the biomedical field.

Highlights

Inhibiting amyloid-β (Aβ ) fibril formation is the primary therapeutic strategy for Alzheimer’s disease
The as-synthesized bulk Bi2Se3 exhibits sheet-like structure with a wide size distribution and is inclined to aggregate together, which was confirmed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) (Supplementary Fig. S2a, b)
The selected area electron diffraction (SAED) pattern (Supplementary Fig. S2c) showed that Bi2Se3 was indexed as a 6-fold symmetry [001] zone axis pattern, which is consistent with the layered structure along the z axis

Summary

Introduction

Inhibiting amyloid-β (Aβ ) fibril formation is the primary therapeutic strategy for Alzheimer’s disease. The interactions between protein and small molecule may be weak[17], resulting in insufficient efficiency to inhibit Aβ aggregation[18]. Small molecules may be accommodated by the highly plastic nature of protein surfaces, decreasing inhibition efficiency[19] To solve these problems, new Aβ inhibitors are in urgent demand. Bismuth selenide (Bi2Se3), a topological insulator, has attracted wide interest in condensed matter physics due to the unique surface electronic states[29,30,31] It consists of stacked layers of a laminated structure held together by weak van der Waals interactions. Bi2Se3 nanoplates can be metabolized after long-term toxicological responses[41] These properties of 2D Bi2Se3 stimulated us to investigate the interaction of 2D Bi2Se3 and Aβ , and explore its ability to inhibit Aβ fibril formation

Methods

Results

Conclusion