Fluorescent gold nanoclusters for in vivo target imaging of Alzheimer's disease

Abstract

Alzheimer's disease involves the formation of numerous senile plaques (SPs) composed of β-amyloid (Aβ) peptides. At the same time the level of various redox-active metal ions changes leading to a completely different redox environment in the brains of Alzheimer's patients compared with the normal brain. Given these considerations, we have explored a new strategy of in vivo rapid fluorescence bio-imaging of Alzheimer's disease through target bio-labeling of the diseased sites. The sites are exposed to aqueous solutions of chloroauric acid (HAuCl₄), which subsequently forms Au salts. These salts then self-assemble into gold nanoclusters (Au NCs), which can then be used for fluorescence imaging. For instance, taking Alzheimer's model mice (AD) and a normal control group of mice (NOR) as models, our studies demonstrate that intravenous injection of aqueous HAuCl₄ through the AD mice tails allowed accurate bright fluorescence labeling around the affected sites of the Alzheimer's brain within a couple of hours, while this did not occur in normal mice (controls): the control mice did not exhibit any fluorescent areas even 24 h after intravenous injection of an identical or larger amount of aqueous HAuCl₄. These observations suggest that HAuCl₄ molecules could readily pass through the blood–brain barrier (BBB) of the AD mice and then mainly accumulate on the hippocampus specific region, followed by in situ biosynthesis of the Au NCs for fluorescent labeling of the affected sites of the Alzheimer's brain. This strategy provides a new method for the rapid and early diagnosis of Alzheimer's disease and may have potential for effective theranostics of Alzheimer's disease.