4.8 Article

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

Journal

ACS APPLIED MATERIALS & INTERFACES
Volume 13, Issue 16, Pages 18581-18593

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c03066

Keywords

ternary chalcogenide materials; copper molybdenum sulfide; amyloid; self-assembly; Alzheimer's disease

Funding

  1. National Research Foundation via the Creative Research Initiative Center, Republic of Korea [NRF-2015R1A3A2066191]

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This study investigates the efficacy of a novel biocompatible ternary chalcogenide nanomaterial, copper molybdenum sulfide (CMS) nanocubes, in dissociating neurotoxic Alzheimer's beta-amyloid (A beta) aggregates under near-infrared (NIR) light. Results demonstrate that NIR-excited CMS nanocubes effectively disassemble A beta fibrils, alleviating their toxicity and reducing A beta plaques in AD mouse brains without causing macroscopic damage. This suggests the potential therapeutic use of CMS nanocubes for Alzheimer's Disease mitigation.
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 (Cu2MoS4, 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 beta-amyloid (A beta) aggregates under NIR light. The accumulation of A beta aggregates in the central nervous system is known to cause and exacerbate Alzheimer's disease (AD). However, clearance of the A beta 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 A beta fibrils by changing A beta fibril's nanoscopic morphology, secondary structure, and primary structure. We have revealed that the toxicity of A beta fibrils is alleviated by NIR-stimulated CMS nanocubes through in vitro analysis. Moreover, our ex vivo evaluations have suggested that the amount of A beta 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.

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