Phosphate Bridged Nickel Metal-Organic Framework-Gold Nanoparticle Composites: A Novel Visualization Therapy for Alzheimer’s Disease

Abstract

Background: Alzheimer’s disease (AD), the most common neurodegenerative disease in the elderly population, is characterized by dementia and neuropsychiatric disorders. Although the pathogenesis of AD remains unclear, most scientists support the amyloid cascade hypothesis that metal ions imbalance accelerates amyloid β (Aβ) aggregation, ultimately resulting in Aβ-induced neurotoxicity. Therefore, metal chelate and Aβ-targeted therapy are considered to be effective strategies for the treatment of AD. Methods: In this study, we fabricated an original nanoparticle composite with the capability to chelate metal ions and disaggregate Aβ fibrils, which consisted of a gold nanoparticle (AuNP) core and a porous metal-organic framework (MOF) shell. In addition, benzothiazolinone (BTA), an ideal fluorescent probe for specific binding of Aβ fibrils, was chosen as a conjugate for the MOF. Results: Results from both in vitro and in vivo experiments revealed that AuNP@MOF-BTA nanocomposites could accurately detect the aggregation and fluorescence imaging of Aβ. Furthermore, it disaggregated Aβ fibrils locally in the near-infrared spectrum as well as inhibited the formation of Aβ aggregates by capturing Cu²⁺ through metal chelation. Therefore, the nanocomposites could, thus, reduce the toxic effects of Aβ aggregation, protect neurons, and improve memory disorders and depressive symptoms. Conclusions: These findings may provide a novel visualization therapy for Alzheimer’s disease guided by fluorescence imaging.