Near-Infrared-Active Copper Molybdenum Sulfide Nanocubes for Phonon-Mediated Clearance of Alzheimer’s β-Amyloid Aggregates

Abstract

Ternary chalcogenide materials have attracted significant interest in recent years because of their unique physicochemical and optoelectronic properties without relying on precious metals, rare earth metals, or toxic elements. Copper molybdenum sulfide (Cu 2 MoS 4 , CMS) nanocube is a biocompatible ternary chalcogenide nanomaterial that exhibits near-infrared (NIR) photocatalytic activity based on its low band gap and electron−phonon coupling property. Here, we study the efficacy of CMS nanocubes for dissociating neurotoxic Alzheimer's β-amyloid (Aβ) aggregates under NIR light. The accumulation of Aβ aggregates in the central nervous system is known to cause and exacerbate Alzheimer's disease (AD). However, clearance of the Aβ aggregates from the central nervous system is a considerable challenge due to their robust structure formed through self-assembly via hydrogen bonding and side-chain interactions. Our spectroscopic and microscopic analysis results have demonstrated that NIR-excited CMS nanocubes effectively disassemble Aβ fibrils by changing Aβ fibril's nanoscopic morphology, secondary structure, and primary structure. We have revealed that the toxicity of Aβ fibrils is alleviated by NIR-stimulated CMS nanocubes through in vitro analysis. Moreover, our ex vivo evaluations have suggested that the amount of Aβ plaques in AD mouse's brain decreased significantly by NIR-excited CMS nanocubes without causing any macroscopic damage to the brain tissue. Collectively, this study suggests the potential use of CMS nanocubes as a therapeutic ternary chalcogenide material to alleviate AD in the future.

Magnetoelectric dissociation of Alzheimer’s β-amyloid aggregates

“…To examine the advent of the magnetoelectrically driven chemical reactions, we tested dihydroethidium (DHE) and terephtalic acid (TA) assays; DHE assay detects the occurrence of 2-hydroxyethidium through the electron transfer reactions and TA assay probes the generation of 2-hydroxyterephthalic acid based on the hole migration process (fig. S7) ( 28 , 35 ). We found that the excited charge carriers were transferred from the surface of BCFO nanoparticles to the reactants (i.e., DHE and TA) approximately 4.2 times more than that of CFO nanoparticles under a low-frequency magnetic field (1 kHz and 13.6 mT) ( Fig.…”

“…Preparation of Aβ fibril solution (40 μM) was carried out with a biocompatible Hepes buffer (pH 7.4) following previous studies ( 26 , 28 ). Morphologies of Aβ fibrils were recorded by an AFM instrument (NNOVA-LABRAM HR800, Horiba, Japan) (with an area of 5 μm by 5 μm and a line number of 512), SEM (S-4800, Hitachi, Japan) at 10 kV, and TEM (Talos F200X, FEI Company, USA) at 200 kV.…”

“…BCFO nanoparticles were uniformly distributed across the entire brain slices during the application of the magnetic field. Then, ThS solution [1 mM in phosphate-buffered saline (PBS) buffer] was applied to the brain slices to stain Aβ plaques for 1 hour and washed with a fresh PBS buffer for three times ( 28 ). Fluorescence images of ThS-stained brain slices were collected by a fluorescence microscope (Eclipse 80i, Nikon, Japan) equipped with a digital camera (DS-Ri2, Nikon, Japan).…”

“…The large-size fluorescent images of the entire brain slices were collected by automatically reassembling multiple small-size snapshots through NIS-Elements software (Nikon, Japan). The fluorescent images were analyzed using ImageJ software (U.S. National Institutes of Health, MD, USA) following the method in our previous study ( 28 ). The density of Aβ plaques was presented with statistical analysis using one-way ANOVA.…”

“…In addition, low-frequency magnetic field has a much lower risk of causing damage to the outer tissues (e.g., scalp and skull) for the deep brain treatment in patients than other physical stimuli, including mechanical vibration (ultrasound), heat radiation (infrared light), and ionizing radiation (x-ray) (23,24). Herein, we propose a previously unknown biomaterial platform using lowfrequency magnetic field that can overcome the potential risk of the conventional approaches [e.g., sonodynamic (25,26), photodynamic (27)(28)(29), radiodynamic (30), and magnetic hyperthermia platforms (31)]. In the current study, we unveil the potential of magnetoelectric materials for low-frequency magnetic field-induced dissociation of toxic A aggregates, a major pathological hallmark of AD.…”