Bifunctional Fluorescent/Raman Nanoprobe for the Early Detection of Amyloid

Abstract

One of the pathological hallmarks of Alzheimer’s disease (AD) is the abnormal aggregation of amyloid beta (Aβ) peptides. Therefore the detection of Aβ peptides and imaging of amyloid plaques are considered as promising diagnostic methods for AD. Here we report a bifunctional nanoprobe prepared by conjugating gold nanoparticles (AuNPs) with Rose Bengal (RB) dye. RB is chosen due to its unique Raman fingerprints and affinity with Aβ peptides. After the conjugation, Raman signals of RB were significantly enhanced due to the surface-enhanced Raman scattering (SERS) effect. Upon binding with Aβ42 peptides, a spectrum change was detected, and the magnitude of the spectrum changes can be correlated with the concentration of target peptides. The peptide/probe interaction also induced a remarkable enhancement in the probes’ fluorescence emission. This fluorescence enhancement was further utilized to image amyloid plaques in the brain slices from transgenic mice. In this study, the RB-AuNPs were used for both SERS-based detection of Aβ42 peptides and fluorescence-based imaging of amyloid plaques. Compared to monofunctional probes, the multifunctional probe is capable to provide more comprehensive pathophysiological information, and therefore, the implementation of such multifunctional amyloid probes is expected to help the investigation of amyloid aggregation and the early diagnosis of AD.

Plasmonic Nanoparticles as Optical Sensing Probes for the Detection of Alzheimer’s Disease

“…Recently, Xia et al have developed bifunctional NPs for detecting and imaging purposes. AuNPs were functionalized with Rose Bengal dye (RB-AuNPs) and allowed the SERS-based in vitro detection of Aβ 1-42 between 0-2 µM, showing high selectivity due to the affinity between RB and Aβ [78]. In addition, confocal imaging of amyloid plaques in brain slices from transgenic mice revealed an age-dependent amyloid deposition [78], consistent with previous studies [79].…”

Review of nanotheranostics for molecular mechanisms underlying psychiatric disorders and commensurate nanotherapeutics for neuropsychiatry: The mind knockout

“…A combined effort of bioinformatics and up-to-date genomic methodologies will decisive in the innovation of these innovative modalities. Surface plasmon resonance approaches to include nanoparticles for the detection of Aβ and, to a lesser extent, of α-synuclein 77 . Nanoplatforms induced gold and silver nanoparticles designed for biomedical applications, especially for the innovation of new strategies for molecular diagnosis with higher analytical capability, sensitivity with the possibility to use for neuropsychiatry 78 .…”

Gold Nanoparticles Mediate Improved Detection of β-amyloid Aggregates by Fluorescence

“…For molecular imaging, new radiotracers, such as the Pittsburg compound B that exhibit affinity for Aβ, have been used [5]. However, this compound contains radioactive 11 C, which is an isotope with low half-life that requires the use of a synchrotron located near the place in which the diagnosis is performed. Thus, because of the high cost associated with the use and implementation of these diagnostic techniques, which is due to the limited accessibility of equipment and the low half-life of the radiotracer, it has been difficult to use them for clinical diagnosis of Alzheimer's disorder.…”

“…Importantly, the scattered light can enhance the fluorescent emission of fluorescent molecules located near, at an optimal distance, to the gold surface. The enhancement of fluorescence by surfaces, which is called surface enhanced fluorescence (SEF), by using plasmon nanoparticles for in vitro detection of biomarkers has been widely described [10]; recently spherical GNPs and the Rose Bengal dye have been used for the detection of Aβ aggregates [11]. However, this last system is not optimal for in vivo applications because the emission of fluorescence is in the visible region and not in the NIR where the tissues exhibit a low absorption of light.…”